Substituted Pyridinones as Modulators of p38 MAP Kinase

18-12-2008 дата публикации
Номер:
AU2007202607B2
Принадлежит: Pharmacia LLC
Контакты:
Номер заявки: 26-20-200707
Дата заявки: 07-06-2007

[1]

The instant invention relates to substituted pyridinones that are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP kinase activity. Pharmaceutical compositions containing the pyridinone compounds, methods of preparing the pyridone, compounds and methods of treatment using the compounds are also disclosed. Description of the Related Art Numerous cell surface receptors use one or more of the mitogen-activated protein kinase (MAP kinase) cascades during signal transduction. MAP kinases are a family of proteindirected serine/threonine kinases that are activated by dual phosphorylation. One subgroup of the MAP kinases is p38 MAP kinase, which is activated by a variety of signals including proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-i (IL-I), as well as bacterial lipopolysaccharides and environmental stress such as osmotic shock and ultraviolet radiation (Ono, K. and J. Han, Cell Signal. 12: i, 2000). Within the p38 kinase family, there are four distinct isozymes: p38 alpha, p38 beta, p38 gamma, and p38 delta. The p38 kinase family function downstream of an activating stimulus by phosphorylating and activating transcription factors (e.g. ATF2, CHOP and MEF2C) as well as other kinases (e.g. MAPKAP-2 and M ?KAP-3) (Trends in Cell biology 7, 353-361, !997;Moi Cell Biology 19, 21-30, 1999; EMBO J 20, 466-479, 2001). Upon activation, the p38 kinase cascade leads to the induction of gene expression of several factors involved in inflammation and immunity including TNF, interleukin-6, granulocyte-macrophage co!ony stimulating factor (GM-CSF), and HIV long terminal repeat (Paul et al., Cell Signal. 9: 403-410j 1997). The products of the p38 phosphorylation stimulate the production of inflammatory cvtokines and other proteins, including TNF and IL-I, and cyclooxygenase-2, and also possibly modulate the effects of these cytokines on their target cells, and thus stimulate inflammation processes (Lee, J.C. et al, Nature, 372: 376, 1994). P38 MAP kinases have also been shown to promote apoptosis during ischemia in cardiac myocytes, which suggests that p38 AP kinase inhibitors can be used to treat ischemic heart disease (J. Biol. Chem. 274, 6272, 1999). They are also required for T-cell HIV-I replication and may be useful targets for AIDS therapy. P38 pathway inhibitors have been used to increase cancer cell sensitivity to cancer therapy also find use in the treatment of asthma (JPET 293, 281, 20OO). TNF is a cytokine and a potent proinflammatory mediator implicated in inflammatory conditions such as arthritis, asthma, septic shock, non-insulin dependent diabetes mellitus, multiple sclerosis, asthma, and inflammatory bowel disease. Thus inhibitors of p38 MAP kinases (required for TNF production) may be useful for the treatment of inflammatory conditions resulting from excessive cytokine production such as arthritis. (Boehm, J.C. and J.L. Adams, Exp. Opin. Ther. Patents i0: 25, 2000, and references cited therein). TNF has also been implicated in viral infections, such as HIV, influenza virus, and herpes virus including herpes simplex virus type-I (HSV-I], herpes simplex virus these (HSV-2), cytomega!ovirus (CMV), variceila-zoster virus (VZV), EpsteinBarr virus, human herpesvirus-6 (HHV-6), human herpesvirus-7 (HHV-7), human herpesvirus-8 (HA -8), pseudorabies and rhinotracheitis, among others. Excessive or unregulated TNF production has also been shown to produce elevated levels of IL-I. Inhibition of TNF, therefore, should reduce levels of !L-I (European Cytokine Netw 6, 225, 1995) and ameliorate disease states caused by unregulated IL-I synthesis. Such disease states include rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis, sepsis, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, adult respiratory distress syndrome, cerebral malaria, chronic pulmonary inflammatory disease, silicosis, pulmonary sarcosis, bone resorption diseases, reperfusion injury, graft versus host reaction, alallograft rejections, fever and myalgias due to infection, cachexia secondary to infection or malignancy, cachexia secondary to acquired immune deficiency syndrome (AIDS), AIDS related complex (ARC), keloid formation, scar tissue formation, Crohn's disease, ulcerative colitis, and pyresis. IL-I has also been shown to mediate a variety of biological activities such as the activation of 'T-helper cells, induction of fever, stimulation of prostaglandin or collagenase production, neutrophil chemotaxis, and the suppression of plasma iron levels (Rev. Infect. Disease, 6, 51 (1984)). Elevated levels of IL-I have also been implicated in mediating or exacerbating a number of disease states including rheumatoid arthritis, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, ulcerative colitis, anaphylaxis, muscle degeneration, cachexia, Reiter's syndrome, type i and type II diabetes, bone resorption diseases, ischemia reperfusion injury, arteriosclerosis, brain trauma, multiple sclerosis, sepsis, septic shock, and toxic shock syndrome. Viruses sensitive to TNF !nhibition, such as HIV-I, H!V-2, HIV-3, are also affected by IL-! production. In rheumatoid arthritis, both IL-I and TNF induce collagenase synthesis and ultimately lead to tissue destruction within arthritic joints (Lymphokine Cytokine Res. (Ii) : 253-256,(1992) and Clin. Exp. Immunol. 989:244-250, (1992)). IL-6 is another pro-inflammatory cytokine, which is associated with many conditions including inflammation. Consequently, TNF, IL-I and IL-6 affect a wide variety of cells and tissues and are important inflammatory mediators of a wide variety of disease states and conditions. The inhibition of these cytokines by inhibition or modulation of p38 kinase is of benefit in controlling, reducing anc alleviating many of these disease states and conditions. Therefore, the present invention concerns finding smal] molecule inhibitors or modulators of p38 kinase and the p3£ kinase pathway. Summary_ of Invention A first aspect of the invention provides for a compound of the Formula I Y 4 H. x; "7 Y 1 or a pharmaceutically acceptable salt thereof, wherein L is -O-; M is -CH 2 -; Xi and X 2 are independently selected from hydroxy(Ci-C 4 )alkyl, H, halogen, alkyl, and R 6 R 7 N-(C|-C 6 alkyl)-; Rs is heteroaryl or heteroarylalkyl, wherein the heteroaryl and heteroaryl groups are optionally substituted with 1,2, 3, or 4 groups that are independently -C(O)NR 6 R 7 , -NR 6 RT, hydroxy(Ci-Ca)alkyl, H, OH, halogen, haloalkyl, alkyl, R 6 R 7 N-(C 1 -C 6 alkyl)-, and -CO 2 -(Ci-C 6 )alkyi; wherein R. 6 and R 7 are independently at each occurrence H, C1-C 6 alkyi, C -C 6 alkoxy CI-C 6 alkyl, CL-C 6 alkoxycarbonyl, OH, CI-C 6 hydroxyalkyl, or C 1 -C 6 alkanoyl, wherein each of the above is unsubstituted or substituted with 1, 2, or 3 groups that are independently, OH or C 1 -C 4 alkyl; and Y, Y 1 , Y 2 , Y 3 , and Y 4 are independently selected from H, halogen and alkyl. The invention also includes the intermediates that are useful in making the compounds of the invention. The compounds bind and/or interact with p38 kinase and/or TNF. Preferably, they inhibit the activity of p38 kinase and/or TNF. They are therefore used in treating p38 map kinase or TNF mediated disorders. Preferably they are used in treating p38 alpha or TNF mediated disorders. A second aspect of the invention provides for a pharmaceutical composition comprising at least one compound of Formula I according to the first aspect of the invention and at least one pharmaceutically acceptable carrier, solvent, adjuvant or excipient. A third aspect of the invention provides for a method of treating a TNF mediated disorder, a p38 kinase mediated disorder, inflammation and/or arthritis in a subject, the method comprising treating a subject having or susceptible to such disorder or condition with a therapeutically-effective amount of a compound of Formula I according to the first aspect of the invention or a pharmaceutically acceptable salt thereof or a pharmaceutical composition according to the second aspect of the invention. A fourth aspect of the invention provides for the use of a compound according to the first aspect of the invention or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating a TNF disorder, a p38 kinase mediated disorder, inflammation and/or arthritis. Detailed Description of the Invention In a preferred aspect, the invent ion provides compound of formula I wherein: when R 2 is benzyloxy, R is H, R 4 is H, and Rs is benzyl o methyl, RI is not hydrogen; no more than two of RI, R 2 , R 4 , and Rs are simultaneousl" hydrogen ; R 6 and Rv are not simultaneously OH; when R 2 is OH, R 4 is methyl and Rs is phenyl, RI is not acetyl and R 4 and Rs are not simultaneously hydrogen. Embodiment 2. Compounds of the formula: R 2 N O l R and the pharmaceutically acceptable salts thereof, wherein RI is H, halogen, alkyl, carboxaldehyde, hydroxyalkyl dihydroxyalkyl, arylalkoxy, arylalkyl, alkenyl, alkynyl arylalkynyl, CN, alkanoyl, alkoxy, alkoxyalkyl haloalkyl, carboxyl, or arylalkanoyl, wherein the aryl portion of arylalkoxy, arylalkyl, ant arylalkanoyl is unsubstituted or substituted with 1 2, 3, 4, or 5 groups that are independently halogen CI-C 4 alkyl, CI-C 4 alkoxy, nitro, CN, ha!oalkyl haloalkoxy or CO 2 R; wherein the alkyl portion of the alkyl, hydroxyalkyl, dihydroxyalkyl, arylalkoxy, arylalkyl, alkanoyl, alkoxy, alkoxyalkyl and arylalkanoyl groups is unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, CI-C 4 alkoxy, CI-C 4 alkoxycarbonyl, or cyclopropyl; is H, OH, halogen, -OSO -(C -C ) a!kyl, -OS0 2 -ary!, arylalkoxy, aryloxy, arylthioalkoxy, ary!a!kynyl, alkoxy, pheny!oxy(C 1-C )alkyl, -OC(O) 4(CH 2 )naryl, -OC(O)N(alkyl) (CH 2 )naryl, alkyl, alkynyl, alkoxyalkoxy, dialkylamino, heteroaryl, heterocycloalkyl aryloxya!ky!, or C0 2 R, wherein each of the above ls unsubstituted or substituted with !, 2, 3, 4, or 5 groups that are independently halogen, -NR 6 R haloalky!, ha!oa!koxy, alkyl, he eroaryl, heteroarylalkyl, - (CI-C 4 ) alkyl-C (0) NR 6 RT, R RvN- (C -C 6 alkyl)-, -C(O)NR 6 RT, - (Ci-C 4 alkyl) -NRC(O)N I 6 R: 7 , CN, hydroxyalkyl, dihydroxyalkyl, -OC (O) NR 6 Rs, or - (C - C 6)alkyI-N(R)-CO 2 R 30, wherein RI and R 1 v are independently H or CI-C alkyl; or RI RI and the nitrogen to which they are attached form a morpho!inyl ring; R 6 and R 7 are independently at each occurrence H, alkyl, hydroxyalkyl, dihydroxyalkyl, alkoxy, alkoxyalkyl, alkanoyl, arylalkyl, arylalkoxy, arylalkoxycarbonyl, or arylalkanoyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, alkoxy, alkyl, OH, SH, carboxaldehyde, haloalkyl, or haloalkoxy; or R RT, and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,Sdioxide, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently C -C 4 alkyl, alkoxycarbonyl, hydroxyl, hydroxyalkyl, dihydroxyalkyl, or halogen; R at each occurrence is independently H or C -C alkyi optionally substituted with 1 or 2 groups that are independently OH, SH, halogen, amino, monoalkylamino, dialkylam£no or C 3 -C 6 cycloalkyl; R 30 is CI-C 6 a!kyl optionally substituted with 1 or 2 groups that are independently OH, SH, halogen, amino, monoalkylamino, dialkylamino or C 3 -C 6 cycloalkyl; H, alkyl optionally substituted with one or two groups that are independently CO 2 R, -COaalkyl, -C(O)NR 6 RT, -C(O)R 6, -N(R 30 )C(O)NRI 6 RI -N(R 30 )C(O)-(Ci-C )alkoxy, or -NR 6 R arylalkoxy, heteroaryl, arylalkyl, hydroxyalkyl, dihydroxyalkyl, haloalkyl, -NRGR - C(O)NR 6 RT, alkoxy, alkoxyalkyl, or alkoxyalkoxy, wherein the heteroaryl or aryl portions of the above are unsubstituted or substituted with i, 2, 3, 4, or groups that are independently halogen, hydroxy, alkoxy, alkyl, -CO -(CI-C 6 )alkyI, -CONR R -NR RT, RONAN-(CI-CG)alkyI-, nitro, haloalkyl, or haloalkoxy; and H, arylalkyl, alkyl optionally substituted with I, 2, or 3 groups that are independently arylalkoxycarbonyl, - NRsRg, halogen, -C(O)NRsRg, alkoxycarbonyl, or alkanoyl, alkoxyalkyl optionally substituted with one trimethylsilyl group, alkoxycarbonyl, amino, hydroxyalkyl, dihydroxyalkyl, alkenyl optionally substituted with alkoxycarbonyl, alkynyl, -SO 2 -alkyl, aryl, alkoxy optionally substituted with one trimethylsilyl group, heterocycloalkylalkyl, heteroarylalkyl, heterocycloalkyl, or heteroaryl, wherein each of the above is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently alkyl, hal ogen, al koxy, aryl a i koxy, hydroxya i kyl, dihydroxyalkyl, thioalkoxy, - SO alkyl, alkoxycarbonyl, arylalkoxycarbonyl, C0 2 R, CN, OH, amidinooxime, NRaRg, R R N-(C 1 -C alky!)-, -C(O)NR R:, ami d i no, hydroxya i kyl, d ihydroxya ! k vl, carboxa!dehyde, -NR 6 R haloalky!, - (C:-C 4 a!ky! ) - C(O)NR 6 RT, - (C=-C 4 alkyl)-CO 2 R, - (Ci-C 4 alkyl)-Ci-C alkoxycarbonyl, - (CI-C 4 alkyl) -CN, - (CI-C 4 alkyl) - NR 15 C (O) R 18 , -O-CH 2 -O-, -O-CH 2 CH 2 -O-, phenyl or haloalkoxy; R 8 is hydrogen, alkyl, alkanoyl, arylalkyi and arylalkanoyl; R 9 is alkyl, aikanoyl, arylalkyl, heteroaryl, aminoalky!, monoalkylaminoalkyl, dia!kylaminoalkyl, and arylalkanoyl. Embodiment 3. Compounds according to embodiment 2 wherein RI is H, halogen, alkyl optionally substituted with CI-C 4 al koxycarbonyl, carboxal dehyde, hydroxyalkyl, dihydroxyalkyl, phenyl (CI-C ) alkoxy, phenyl (C 1 -C 6 ) alkyl, CN, al kanoyl, a i koxy, C 2 -C 4 al kynyl, C 2 -C a i kenyl optionally substituted with CI-C 4 al koxycarbonyl, alkoxyalkyl, haloalky!, or phenyl(C 1 -C 6 )alkanoyl, wherein the phenyl groups are unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently halogen, CI-C 4 alkyl, CI-C 4 alkoxy, nitro, CN, CF 3 , OCF 3 or CO, R; wherein the alkyl groups are unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, methoxy, or ethoxy; R 2 is OH, phenyl(C 1 -C )alkoxy, phenyloxy, phenyloxy(C 1 -C )alkyl, phenyl (CI-C ) thioalkoxy, C 1 -Cs alkoxy, alkoxyalkoxy, -OSO 2 phenyl, a!kynyl, phenyl (C 2 -C 4 ) alkynyl, alkyl, -OC (0) NH (CH 2 ) npheny!, -OC (0) N (a!kyl) (CH 2 ) henyl, dialkyl amino, pyridyl, pyrimidyl, pyrida=yl, pyrazolyl, imida zo! yl, pyrro! yl, t e t rahydrcqu i no i i ny i, tetrahydroisoquinol inyl, tetrazo!y!, pyrazinyl, benzimidazolyl, triazinyl, tetrahydrofuryl, piperidinyl, hexahydropyrimidinyl, thiazo!yl, thieny!, or C0 2 R, wherein n is 0, i, 2, 3, 4, 5 or 6; each of the above is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently halogen, NR R hal oal kyl, ha I ca i koxy, hydroxyal kyl, dihydroxyalkyl, alkyl, phenyl, pyridyl, piperidinyl, piperazinyl, - (CI-C 6 ) alkyi-N (R) -C0 2 R 30 , R 6 RTN- (CI-C 6 alkyl)-, -C(O)NR 6 R - (CI-C 4 )a!kyI-C(O)NR R -(CI-C 4 alkyl-NRC(O)NRI6 6 RIv, or -OC(O)NR 6 R wherein R 6 and R are independently at each occurrence H, al kyl, ( CI - C 4 ) hydroxya i kyl 1 ( C 1 - C 4 ) dihydroxyalkyl,(Ci-C 4) alkoxy, (Ci-C 4 ) alkoxy (CI-C 4) alkyl,(C 1-C 4) alkanoyl, phenyl (Q-C 4 ) alkyl, phenyl(Ci-C 4) alkoxy, phenyl (Ci-C 4 ) alkoxycarbonyl, or phenyl (CI-C 4 ) alkanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, OH, SH, C 3 -C cycloalkyl, (CI-C 4 ) alkoxy, (CI-C 4 ) alkyl, CF 3 , carboxaldehyde, NH 2 , NH (Ci-C 6 ) alkyl, N (CI - C )alkyl (Ci-C 6 )alkyl, OCF 3 ; or R 6, RT, and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, piperidinyl, pyrro!idinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalky!, C 1 -C 4 alkoxycarbony!, or halogen; and H, alkyl optionally substituted with one or two groups zhat are independently C0 2 R, -COzaiky!, -C(O)NR 6 RT, -C(O)R 6, -N(R 30 )C(O)NR! 6 R 17 , -N(R 30 )C(O)-(C 1 -C )alkoxy, or -NR RT, -C(O)NR R phenyl(C:-C )alkoxy, phenyl(C 1 - C )alkyl, hydroxyalkyl, dihydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, or alkoxyalkoxy, wherein the phenyl groups are unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, CF 3 , OCF ; is phenyl(C 1-C 6)alkyl, (C 1 -C )alkyl optionally substituted with I, 2, 3, 4, or 5 groups that are independently phenyl Ci-C 4 alkoxycarbonyl, -NRsRg, halogen, -C(O)NRsRg, alkoxycarbonyl, or alkanoyl, phenyl, alkoxy, C 2 -C alkynyl, C 2 -C 6 alkenyl optionally substituted with alkoxycarbonyl, indolyl, quinolinyl, isoquinolinyl, isoindolyl, dihydroindolyl, pyrazolyl, imidazolyl, dihydroisoindolyl, indolon-2-yl, indazolyl, benzimidazolyl, pyridyl, imidazolidine dione, pyrazolyl (Ci-C 6 alkyl) , imidazolyl(C 1-C alkyl), piperidinyl (CI-C ) alkyl, pyrrolidinyl(Ci-C 6)alkyl, imidazolidinyl (CI-C 6 ) alkyl, tetrahydroisoquinolinyl(C 1C ) alkyl, iH-indazolyl (CI-C 6 ) alkyl, dihydroindolon-2yl (C 1 -C alkyl) , indolinyl (Ci-C 6 alkyl ) , dihydrobenzimidazolyl (C 1 -C alkyl) , or dihydrobenzoimidazolonyl (CI-C alkyl ) , pyridyl(C 1-C ) alkyl, pyridazinyl (CI-C ) alkyl, pyrimidinyl(C 1-C ) alkyl, pyrazinyl (Ci-C 6 ) alkyl, tetrahydrofuryl(C 1 - C 6)alkyl, naphthyl(C 1 -C 6 )alkyl, morpholinyl (CI-CG) alkyl, tetrahydrofuryl (Ci-C 6 ) alkyl, thienyl (Ci-C 6 ) alkyl, piperazinyl (CI-C 6 ) alkyl, indolyl (CI-CG) alkyl, quinolinyl (CI-C 6 ) alkyl, isoquinolinyl (CI-C 6 ) alkyl, isoindolyl (Ci-C 6 ) alky!, dihydroindoly! (C:-C 6 ) alkyl, pyrazolyl (C -C 4 ) a!ky!, imidazolyl (C- -C ) a!kyl, dihydroisoindoly! (C!-C 6 ) alkyl, indoon-2-yl (C 1 -C ) alkyl, indolon2-yl (CI-C 6 ) alky!, or morpho! inyl C 1 -C alkyl, wherein each of the above is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently CI-C 6 alky!, halogen, C:-C alkoxy, phenyl C 1 -C alkoxy, CI-C thioalkoxy, Ci-C 6 alkoxycarbonyl, C0 2 R, CN, -SO 2 (C 1 - C 6)alkyl, amidinooxime, NRsRg, -NRGR NR R 7 CI-C alkyl, -C (O) NR 6 RT, - (CI-C 4 ) alkyl-C (0) NR 6 RT, amidino, CI-C 4 haloalkyl, hydroxy CI-C 6 alky!, CI-C 6 dihydroxyalkyl, or CI-C 4 haloalkoxy; wherein R 8 is hydrogen, C 1 -C alkyl, CI-C 6 alkanoyl, phenyl C 1-C alkyl and phenyl C 1 -C alkanoyl; and R 9 is aminoalkyl, mono C 1 -C alky!amino CI-C alkyl, di CI-C alkylamino CI-C 6 alkyl, CI-C 6 alkyl, CIC alkanoyl, phenyl C 1 -C alky!, indazolyl, and phenyl CI-C alkanoyl. Embodiment 4. Compounds according to embodiment 3, where in H, halogen, CI-C 4 alkyl optionally substituted with CI-C alkoxycarbonyl, C 2 -C 4 alkenyl optionally substituted with CI-C 4 alkoxycarbonyl, C 2 -C 4 alkynyl, or carboxaldehyde; is benzyloxy, OH, phenyloxy, phenyloxy(Ci-C 6 )alkyl, pheny] (CI-C 4) thioalkoxy, or pyridyl; wherein each of the above is optionally substituted with i, 2, 3, 4, or 5 group[ that are independently halogen, -(CI-C 6 )alkyI-N(R)-CO 2 R 30 , NR R 7, - (CI-C 4 ) alkyl -C (O) NEGRO (CI-C 4 ) haloalkyl, -C(O)NR 6 Rv, - (CI-C 4 alkyI)-NRC(O)NRI 6 RIv, (CI-C 4 ) haloalkoxy, hydroxyalkyl, CI-C dihydroxyaikyl, (CI-C 6 ) alkyl, pyridyl, Embodiment 4a. Compounds according to embodiment 4, wherein R is H. Embodiment 4b. Compounds according to embodiment 4, wherein R= is halogen. Embodiment 4c. Compounds according to embodiment 4, wherein RI is CI-C 4 alkyl optionally substituted with Ci-C a!koxycarbonyl. Embodiment 5. Compounds according to embodiment 4, wherein Rs is indolyl, pyridyl, pyridazinyl, pyrimidinyl, indazolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, pyrazolyl, imidazolyl, furanyl, quinolinyl, isoquinolinyl, isoindolyl, dihydroindolyl, dihydroisoindolyl, indolon-2y!, or pyrazinyl, each of which is unsubstituted or substituted with i, 2, 3, 4 or 5 groups that are independently CI-C 4 alkyl, halogen, CF 3 , OCF 3 , -CO 2 CH 3 , CICA hydroxyalkyl, dihydroxyalkyl, CI-C 4 alkoxy, -COz(CI-Cs alkyl) , benzyloxy, -NR RT, - (CI-C 4 ) alkyl-C (O) NR R -NRsRg, NR Rv-(CI-C 4 alkyl), -C(O)NR 6 Rv, or amidinooxime; wherein R and R are independently at each occurrence H, CI-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C 4 dihydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkoxy CI-C 4 alkyl, CI-C 4 alkanoyl, phenyl CI-C 4 alkyl, phenyl CI-C 4 alkoxy, or phenyl CIC 4 alkanoyl, wherein each is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, OH, SH, C 3 -CG cycloalkyl, aryl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF or OCF 3 ; or R 6 , Rv, and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy C:-C alky!, CI-C dihydroxyalkyl, or halogen. Embodiment 6. Compounds according to embodiment 5, wherein Rs is indolyl, pyridyl, pyrimidinyl, pyrazolyl, furanyl, indazolyl, dihydroindoly!, dihydroisoindolyl, indolon-2yl, or pyrazinyl, each of which is unsubstituted or substituted with !, 2, 3, or 4 groups that are independently CI-C 4 alkyl, halogen, CF 3 , OCF], -CO 2 CH 3 , C - C 4 hydroxyalkyl, CI-C 4 dihydroxyalkyl, CI-C 4 alkoxy, - CO 2(CI-C 5 alkyl) , benzyloxy, -C (O) NR RT, -NRsRg, -(CIC 4)alkyI-C(O)NR 6 Rv, -NR 6 RT, NR 6 R -(CI-C 4 alkyl)-, and amidinooxime. Embodiment 7. Compounds according to embodiment 6, wherein Rs is indolyl, pyridy!, pyrimidinyl, dihydroindolyl, dihydroisoindolyl, pyrazolyl, or pyrazinyl, each of which is unsubstituted or substituted with I, 2, 3, or 4 groups that are independently CI-C 4 alkyl, halogen, CF 3 , OCF 3 , -CO 2 CH 3, CI-C 4 hydroxyalkyl, CI-C 4 dihydroxyalkyl, CI-C 4 alkoxy, -CO 2 (CI-Cs alkyl) , benzyloxy, -C (O)NR 6 R NRsRg, (CI-C 4) alkyl-C (O) NR R -NR 6 R NR RT- (CI-C 4 alkyl ) -, or amidinooxime; wherein R and Rv are independently at each occurrence H, CI-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C 4 dihydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkanoyl, CI-C 4 alkoxy CI-C 4 alkyl, each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF 3 , or Embodiment 8. Compounds according to embodiment 7, wherein Rs is indo!yi, pyridyl, pyrimidinyi, dihydroindolyl, dihydroisoindolyi, pyrazolyl, or pyraniny!, each of which is unsubstituned or substituted with I, 2, or 3 groups that are independently CI-C 4 alkyl, halogen, CF OCF CIC 4 hydroxya i ky!, CI-C 4 dihydroxyal kyl, C -C 4 al koxy, -C(O)NR 6 RT, - (CI-C 4 )alkyI-C(O)NR 6 RT, NRsRg, -NR 6 Rv, or NR 6 Rv- (CI-C 4 alkyl) -; wherein R 6 and R 7 are independently at each occurrence H, C=-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C dinydroxyalkyl, CI-C 4 alkanoyl, or CI-C 4 alkoxy, each of which is optionally substituted with I, 2, or 3 groups that are independently halogen, OH, SH, C -C 6 cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF or OCF 3 . Embodiment 9. Compounds according to embodiment 4, wherein R 5 is phenyl, phenyl(Ci-C 6 )alkyl, or (Ci-C 6 )alkyl, wherein each of the above is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently alkyl, ha!ogen, alkoxy, benzyloxy, hydroxyalkyl, dihydroxyalkyl, thioalkoxy, -CO 2 (C -Cs alkyl) , CO 2 R, CN, amidinooxime, -NR,Rg, -NR Rv, R 6 RvN- (CI-C 6 alkyl) -, -C (O) NR 6 R -(CI-C 4 )alkyI-C(O)NR 6 RT, amidino, CF 3 , or OCF 3 ; R 8 is hydrogen, CI-C alkyl, CI-CG alkanoyl, phenyl C -C 6 alkyl and phenyl C -C 6 alkanoyl; and R 9 is aminoalkyl, mono CI-C 6 alkylamino CI-C 6 alkyl, di CIC alkylamino CI-C 6 alkyl, CI-C 6 alkyl, CI-C 6 alkanoyl, phenyl CI-C 4 alkyl, indazolyl, and phenyl C 1 -C 4 alkanoyl. Embodiment I0. Compounds according to embodiment 4, wherein Rs is phenyl, phenyl (Ci-C 6 )alkyl, which is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently alkyl, halogen, alkoxy, benzyloxy, thioalkoxy, -CO (CI-C alkyl), CO 2 R, CN, amidinooxime, NRsRg, -NR R R 6 RTN- (CI-Ce alkyl)-, R R NC(O)- (CI-C 4 alkyl)-, ReRTNC(O)-(Cs-Ce alkyl)-, -C(O)NR RT, amidino, CF 3 , or OCF ; wherein Re and R are independently at each occurrence H, CI-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C 4 dihydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkoxy CI-C 4 alkyl, CI -C 4 alkanoyl, phenyl CI-C 4 alkyl, phenyl CI-C 4 alkoxy, or phenyl CIC 4 alkanoyl, wherein each is unsubsti tuted or substituted with i, 2, or 3 groups that are independently, halogen, OH, SH, C 3 °C 6 cycloalkyl, CIC 4 alkoxy, CI-C 4 alkyl, CF or OCF 3 ; or Re, R and the nitrogen to which they are attached form a morpholinyl, thiomorphol inyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalkyl, or halogen; R 8 is hydrogen, CI-C 6 alkyl, C 1 -C alkanoyl, phenyl CI-CG alkyl and phenyl CI-C 6 alkanoyl; and R 9 is aminoalkyl, mono CI-C 6 alkylamino CI-C alkyl, di CIC alkylamino CI-C 6 alkyl, CI-C alkyl, CI-C 6 alkanoyl, phenyl CI-C 4 alkyl, indazolyl, and phenyl CI-C 4 alkanoyl. Embodiment ii. Compounds according to embodiment I0, wherein Rs is phenyl, benzyl or phenethyl, wherein each is optionally substituted with i, 2, 3, 4, or 5 groups that are independently C:-C 6 alkyl, -NR RT, -C (O) NR R - (C 1 -C alkyI)-C(O)NR RT, -NRsR halogen, CI-C alkoxy, CO 2 R, - (C - C alkyl)-CO 2 R, C!-C 6 thioalkoxy, amidinooxime, CI-C 6 a!koxycarbony!, -(CI-C alky!)-C:-C 6 a!koxycarbonyl, CI-C hydroxyalkyl, C:-C dihydroxya!kyl, -(C -C 4 a!kyl)-CN, CN, phenyl C 1 -C 6 a!koxy, OH, CI-C 4 haloalky!, C=-C haloalkoxy, R 6 R N- (CI-C 6 aiky!) -, - (CI-C 4 a!kyl)-NR sC(O)Ris, amidinooxime, -S0 2 (CI-C 6 a!kyl), -O-CH=-O-, -O-CHoCH -O-, phenyl CI-C 4 alkoxy, or phenyl; wherein R and R are independently at each occurrence H, CI-C 4 alkyl, CI-C hydroxyalkyl, C 1 -C 4 dihydroxyalkyl, CI-C 4 alkanoyl, or CI-C 4 alkoxy, each of which is optionally substituted with I, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF 3 , or OCF 3 . Embodiment 12. Compounds according to embodiment ii, wherein Rs is phenyl, benzyl or phenethyi, each of which is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently CN, halogen, CI-C 4 alkoxy, CF 3 , OCF 3, CI-C 4 alkyl, -NRsRg, -NR 6 RT, R 6 R N-(CI-C 6 alkyl)-, or -C(O)NR 6 R wherein R and R are independently at each occurrence H, C 1 -C alkyl, CI-C 4 hydroxyalkyl, CI-C 4 dihydroxyalkyl, Ci-C 4 alkanoyl, or CI-C 4 alkoxy, each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF 3 , or OCF 3 . Embodiment 13. Compounds according to embodiment 4, wherein the Rs group is of the formula: wherein Z: and Z 2 are independently H, halogen, C -C alky!, or CO 2 R; and Z is -C (O) NR 6 RT, - (C 1 -C 4 )a!kyl-C(O)NR 6 RT, - (C 1 -C alkyl)- NRIsC (0) R 18 , -NR 6 R R 6 R N- (CI-C 6 alkyl) -, -NRsRg, CI-C 6 hydroxyalkyl, C 1 -CG dihydroxyalkyl, CI-C 6 alkyl, C0 2 R, or halogen; wherein R 6 and Rv at each occurrence are independently H, OH, CI-C 6 alkyl, amino Ci-C 4 alkyl, NH(CI-C alkyl)alkyl, N(CICG alkyl)(C 1 -CG alkyl) CI-C alkyl, C 1 -C hydroxyalkyl, CI-C 6 dihydroxyalkyl, CI-C 6 alkoxy CI-C 6 a!kyl, or SO 2 (C 1 -C alkyl) each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 a!koxy, CI-C 4 alkyl, OH, CF 3, or OCF 3 ; or R R and the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, piperazinyl, or a morpholinyl, thiomorphol inyl, ring optionally substituted with 1 or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 alkyl, C -C 4 dihydroxyalkyl, or halogen; and RiB is CI-C alkyl optionally substituted with -O- (C 2 -C 6 alkanoyl, CI-C hydroxyalkyl, CI-C 4 dihydroxyalkyl, C -C alkoxy, C -C alkoxy C -C 6 alkyl; amino CI-C 6 alkyl, mono or dialkylamino CI-C 6 alkyl. Embodiment 14. Compounds according to embodiment 4, wherein is pyrazolyl(C--C 6 alkv!), imidazoiyl C:-C alkyl) thienyl(C 1-C alky!), furanyl(C--C alky!), piperidinyl (C 1 C 6) alkyl, pyrrolidinyl (Ci-C 6 )alkyl, imlda=clidlny! (C:- C )alkyl, piperazinyl(C -C )a!kyl, pyridyl(C:-C )alky!, pyrimidyl(C 1-C 6)a!kyl, pyridazy!(C -C 6 )alkyl, pyrazinyi(C 1 C 6) alkyl, isoquino!inyl (C 1 - C ) alkyl, tetrahydroisoquinolinyl (CI-C 6 ) alkyl, indo!y! (CI-C 6 ) a!kyl, IH-indazoly! (CI-C 6 ) alkyl, dihydroindo!yl (C 1 -C alky!) dihydroindolon-2-yl (CI-C 6 alkyl) , indolinyl (C!-C 6 alky!) , dihydroisoindolyl (CI-C 6 alkyl) , dihydrobenzimdazolyl (CI-C alkyl), or dihydrobenzoimidazolonyl(C!-CG alkyl), wherein each of the above is unsubstituted or substituted with !, 2, 3, 4, or 5 groups that are independently (C - CG)alkyl, halogen, (Q-C 6 )alkoxy, (C 1 -C 6 )hydroxyalkyl, C 1-C dihydroxyalkyl, phenyl (C -C ) alkoxy, (C 1 - C 6) thioalkoxy, (C 1 -C ) alkoxycarbonyl, phenyl (C 1 - C 6)alkoxycarbonyl, OH, C0 2 R, CN, amidinooxime, -NRBRg, -NR R R 6 R N- (C -C 6 a!kyl) -, -C (O) NR RT, - (Ci-C 4 alkyl)-C(O)NR 6 Rv, amidino, piperaziny!, morpholinyl, - SO (Ci-C 6 ) alkyl, - S0 2 NH 2 , - S0 2 NH (CI-CG) alkyl, - SO 2 N (CI-C ) alkyl (CI-C ) alkyl, (CI-C 4 ) haloalkyl, - (CIC 4 alkyl) -NRIsC (O)NRI RIv, - (CI-C 4 alkyl) -NRIsC (0) R 18 , -O-CH 2-O, -O-CH 2 CH 2 -O-, or (CI-C 4 )haloalkoxy; wherein Re and R are independently at each occurrence H, (CI-C ) alkyl, (CI-C 6 ) alkoxy, (CI-CG) alkoxy (CIC ) alkyl, (CI-C ) alkoxycarbonyl, (C - C ) hydroxyalkyl, C -C dihydroxyalkyl, - (C - C ) alkyl-CO - (C -C ) alkyl, (C -C ) alkanoyl, phenyl (C -C ) alkyl, phenyl (C -C ) alkoxy, or phenyl(C -C )alkanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, (C - C )alkoxy, OH, SH, C -C cycloalkyl, NH NH(C - Re, R and the nitrogen to which they are attached form a morphol inyl, thiomorphol inyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy C -C 4 a!kyl, C:-C 4 dihydroxyalkyl, or halogen; and R 18 is Ci-C alkyl optionally substituted with -0-(C 2 - C alkanoyl, CI-C hydroxyal kyl, C 1 -C dihydroxyalkyl, CI-C 6 alkoxy, CI-C alkoxy CI-C alkyl; amino CI-C alkyl, mono or dialkylamino CI-C 6 alkyl. In this embodiment, it is preferred that R 6 and R 7 are not simultaneously OH; and Re and R 7 are not simultaneously -SO (C 1 -C 6 alkyl) . Embodiment 15. Compounds according to embodiment 14, wherein alkyl) , imidazolyl (CI-CG alkyl) , Rs is pyrazolyl (CI-C 6 alkyl) , thienyl (C 1 -C alkyl) , benzimidazolyl (C 1 -C indolyl (C,-C 6 alkyl ) , pyrimidyl (CI-CG) alkyl, alkyl) , dihydroisoindolyl (CI-C dihydroindolyl (CI-C 6 alkyl) , dihydroindolon-2-yl (Ci-C 6 alkyl) , pyridinyl (CI-C alkyl), piperazinyl(C 1 -C alkyl), or pyrazinyl(CI-C 6 alkyl) each of which is optionally substituted with i 0 2, or 3 groups that are independently CI-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C 4 dihydroxyalkyl, halogen, -C (O) NR 6 R - (CI-C 4 alkyl-C(O)NR6RT, 6 RT, CI-C alkoxycarbonyl, -NR 6 RT, R 6 RTN- (CI-C alkyl)-, haloalkyl, C 1 -C alkanoyl, R 6 and R 7 at each occurrence are independently H, C -C 6 alkyl optionally substituted with I, 2, or 3 groups that are independently C:-C 4 alkoxycarbonyi, halogen, C -C cycloalkyl, OH, SH, or CI-C alkoxy; or R Rv, and the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, piperazinyl, cr a morpholinyl ring optionally substituted with i or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalkyl, or halogen. Embodiment 16. Compounds according to embodiment 15, wherein Rs is of the formula: wherein Zs is CI-C 4 alkyl, Ci-C 4 hydroxyalkyl, Ci-C 4 dihydroxyalkyl, halogen, -C (0) NR 6 RT, - (Ci-C 4 alkyl) -C (O) NR RT. C 1 -C alkoxycarbonyl, R 6 RTN-(CI-C 6 alkyl-, -NR 6 Rv, CF 3 , or CI-C alkanoyl, wherein R 6 and Rv at each occurrence are independently H, C -Cs alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C alkoxycarbonyl, halogen, C 3-C 6 cycloalkyl, OH, SH, or CI-C 4 alkoxy; or R 6, RT, and the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, piperazinyl, or a morpholinyl ring optionally substituted with 1 or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalkyl, or halogen. Embodiment 17. Compounds according to embodiment 15, wherein R 5 is of the formula: wherein Z is CI-C 4 alkyl, Ci-C 4 hydroxyalkyl, C 1 -C dihydroxyalkyl, ha!ogen, -C (O) NR R - (C -C 4 alkyl) -C (O) N RGRT. Ci -C alkoxycarbonyl, R 6 R N-(CI-C 6 alky!)-, -NR RT, CF 3 , or CI-C alkanoyl, wherein R 6 and Rv at each occurrence are independently H, CI-C alkyl optionally substituted with I, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-C 6 cycloalkyl, OH, SH, or CI-C alkoxy; or Re, RT, and the nitrogen to which they are attached fom a piperidinyl, pyrro!idinyl, piperazinyl, or a morpholinyl ring optionally substituted with I or 2 groups that are independently alkyl 0 hydrox Y, hydroxy CI-C 4 alkyl, CI-C¢ dihydroxyalkyl, or halogen. Embodiment 18. Compounds according to either embodiment 16 or 17, wherein Z 5 is CI-C 4 alky!, CI-C 4 hydroxyalkyl, CI-C 4 dihydroxyalkyl, halogen, CI-C alkoxycarbonyl, CF 3 , or CI-C alkanoyl. Embodiment 19. Compounds according to either embodiment 16 or 17, wherein Zs is C -C 4 alkyl, -C (O) NEGRO -(CI-C alkyI)-C(O)NR 6 Rv, R 6 RTN-(CIC alkyl) -, or -NR 6 Rv, CF or CI-C 4 alkanoyl, wherein RG and R at each occurrence are independently H, CI-C 6 alkyl optionally substituted with i, 2, or 3 groups -hat are independently C -C 4 alkoxycarbonyl, halogen, C 3-C 6 cycloalkyl, OH, SH, or CI-C 4 alkoxy; R R and the nitrogen to which they are attached form a piperidinyl, pyrrolidiny!, Dinerazinyl, or a morpholinyl ring optionally substituted with i er 2 groups that are independently alkyl, hydroxy, hydroxy C:-C alkyl, CI-C 4 dihydroxyalkyl, or halogen. Embodiment 20. Compounds according to embodiment 19, wherein Zs is -C(O)NR 6 R -(CI-C 4 alkyl)-C(O)NR 6 RT, R 6 RTN- (CI-C alkyl)-, or -NR 6 R wherein R 6 and R 7 at each occurrence are independently H, C 1 -C a!kyl optionally substituted with i, 2, or 3 groups that are independently CI-C a!koxycarbonyl, halogen, cyclopropyl, OH, SH, or CI-C 4 alkoxy. Embodiment 21. Compounds according to embodiment 15, wherein ZI 0 Rs is of the formula: <iZ 20 , wherein Z 10 is H or methyl; and Z 20 is hydroxy (CI-C 4 ) alkyl, CI-C 4 dihydroxyalkyl, OH, halogen, haloalkyl, (Ci-C 4 )alkyl, OCF 3 , -NR 6 R R 6 RvN- (CI-C alkyl) -, - (CI-C 4 alkyl) -C (O) NR RT, or -C (O) NR 6 Rv, wherein R 6 and R 7 at each occurrence are independently H, CI-C 6 alkyl optionally substituted with I, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-C 6 cycloalkyl, OH, SH, or CI-C 4 alkoxy. Embodiment 22. Compounds according to embodiment 1 5, wherein Z I "r<" N/ " Z 20 wherein Rs is of the formula: Z 10 is H or methyl; and Z 20 is hydroxy (C -C ) alkyl, CI-C 4 dihydroxyalkyl, OH, halogen, CF 3 , (Ci-C 4 ) a!kyl, OCF 3 , -NR RT, R 6 R N- (C,_-C alkyl)-, - (CI-C 4 alkyl-C(O)NR6RT, 6 RT, or -C(O)NR 6 R wherein R 6 and R at each occurrence are independently H, CI-C 6 alkyl optionally substituted with i, 2, or 3 groups that are independently Ci-C 4 alkoxycarbonyl, halogen, C]-C cycloalkyl, OH, SH, or CI-C 4 alkoxy. Embodiment 23. Compounds according to embodiment 15, wherein Z R 5 is of the formula: Z2o, wherein Z 10 is H or methyl; and Z 20 is hydroxy (CI-C 4 ) alkyl, CI-C 4 dihydroxyalkyl, OH, halogen, haloalkyl, (Ci-C 4 )alkyl, OCF -NR 6 RT, R 6 R N-(CI-C alkyl) -, - (CI-C 4 alkyl) -C (0) NR R or -C (O) NR 6 R wherein R 6 and Rv at each occurrence are independently H, CI-C alkyl optionally substituted with I, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-C 6 cycloalkyl, OH, SH, or C -C 4 alkoxy. Embodiment 24. Compounds according to embodiment 15, wherein / "N" "Z20, wherein Rs is of the formula: Z!o is H or methyl; and Z 20 is hydroxy (C-- C 4 ) a!kyl, C 1-C dihydroxyalkyl, O14, halogen, CF (C -C ) alkyl, OCF 3, -NR 6 R R R N- (C!- C a!kyl) -, - (C -C 4 alkyl) -C(O)NRGRT, or -C (O) NR 6 R wherein R 6 and R at each occurrence are independently H, C:-C alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 aikoxycarbonyl, halogen, C 3-C cycloa!kyl, OH, SH, or CI-C 4 alkoxy. Embodiment 25. Compounds according to embodiment 15, wherein Z Rs is of the formula: --Z20, wherein Z 10 is H or methyl; and Z 20 is hydroxy (CIC 4 ) alkyl, Cz-C 4 dihydroxyalkyl, OH, halogen, haloalkyl, (C 1 -C 4 )alkyl, OCFs, -NR 6 RT, R 6 R?N-(CI-C 6 alkyl) -, - (C 1 -C alkyl)-C (O) NR 6 R or -C (O) NR 6 RT, wherein RG and Rv at each occurrence are independently H, CI-C alkyl optionally substituted with i, 2, or 3 groups that are independently Cz-C 4 alkoxycarbonyl, halogen, C 3-C 6 cycloalkyl, OH, SH, or C -C 4 alkoxy. Embodiment 26. Compounds according to embodiment 15, wherein Z .</ J Z 20, wherein Rs is of the formula: Z 10 is H or methyl; and Z 0 is hydroxy (Ci -C 4 ) alkyl, C!-C dihydroxya!kyl, OH, halogen, CF 3 , (Ci-C 4 ) alkyl, OCF 3 , -NR 6 RT, R 6 R N- (CI-C 6 alkyl-, -(CI-C 4 alkyl-C(O)krR RT, 0 r-C(O)NR 6 R , wherein R 6 and R 7 at each occurrence are independently H, CI-C 6 alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C -C 6 cycloalkyl, OH, SH or CI-C 4 alkoxy. Embodiment 27. Compounds according to embodiment 15, wherein Z Rs is of the formula: Z20, wherein Z 10 is H or methyl; and Z 20 is hydroxy (CI-C 4 ) alkyl, CI-C 4 dihydroxyalkyl, OH, halogen, haloalkyl, (Ci-C 4 )alkyl, OCF 3 , -NR Rv, R 6 RTN-(CI-C alkyl)-, - (CI-C 4 alkyl)-C(O)NR 6 Rv, or -C(O)NR 6 Rv, wherein R and Rv at each occurrence are independently H, CI-C 6 alkyl optionally substituted with I, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-C cycloalkyl, OH, SH, or CI-C 4 alkoxy. Embodiment 28. Compounds according to embodiment 15, wherein Z Z 20 , wherein Rs is of the formula: Z 10 is H or methyl; and Z 0 is hydroxy (C:-C ) aikyl , Ci-C 4 dihydroxya!kyl, OH, halogen, CF 3 , (Ci-C ) alkyl, OCF -N R 6 R R R=N- (C:-C alky!)-, -(C 1 -C 4 a!kyl)-C(O)NR 6 R:, or-C(O)NR RT, wherein R 6 and R at each occurrence are independently H, C -C alkyl optionally substituted with i, 2, or 3 groups that are independently C -C a!koxycarbonyl, halogen, C 3 -C 6 cycloa!kyl, OH, SH, or CI-C 4 alkoxy. Embodiment 29. Compounds according to embodiment 4, wherein Rs is pheny!, which is optionally substituted with I, 2, 3, 4, or 5 groups that are independently C -C 4 alkyl, -C(O)NR 6 RT, - (CI-C 4 alkyI)-C(O)NR 6 RT, -NR 6 RT, NR 6 RT(CI-C 6 alkyl) , CI-C 6 hydroxyalkyl, dihydroxyalkyl, halogen, CI-C 4 alkoxy, CO 2 R, OH, C: -C alkoxycarbonyl, CF 3 , - (CI -C 4 alkyl ) - NR!sC(O)NRI 6 R 17, -(C 1 -C 4 alkyl)-NR 1 sC(O)R 16 ; wherein R s is H or C -C alkyl; R 16 and R 17 are independently H or CI-C alkyl; or RI R 1 v, and the nitrogen to which they are attached form a morpholinyl ring; and R 18 is CI-C 6 alkyl optionally substituted with -O-(C 2 -C 6 alkanoyl, CI-C 6 hydroxyal kyl, CI-C 6 dihydroxyalkyl, CI-C 6 alkoxy, CI-C 6 alkoxy CI-C alkyl; amino CI-C 6 alkyl, mono or dialkylamino CI-C 6 alkyl. Embodiment 30. Compounds according to embodiment 29, wherein Rs is of the formula: ZI is H, halogen, C 1 -C 4 alkyl, CI-C 4 haloalkyl, C -C hydroxyalkyl, CI-C 4 dihydroxyalkyl, or CI-C 4 alkoxy; and Z 2 is CI-C 4 alkyl, -C (O) NR 6 R - (CI-C 4 alkyl-C(O)NR R -NR 6 RT, hTR 6 R (C - C 6 alkyl ) , C - C 6 hydroxyalkyl, C: - C 6 dihydroxyalkyl, halogen, CI-C 4 alkoxy, CO R, OH, C 1 -C 6 alkoxycarbonyl, or C 1 -C 4 haloalkyl; Z is H, CI-C 4 a!kyl, -C(O)NR 6 R -(C:-C 4 alkyl)-C(O)NR 6 RT.-NR6Rv, NEGRO (Ci - C alkyl ) , Ci -C 6 hydroxyalkyl, Ci - C 6 dihydroxyalkyl, halogen, CI-C 4 alkoxy, CO 2 R, OH, CI-C 6 alkoxycarbonyl, or Ci-C 4 haloalkyl; and wherein R and Rv at each occurrence are independently H 0 OH, CI-C 6 alkyl, amino C -C 4 alkyl, NH (CI -C 6 alkyl ) alkyl, N (CiCG a!kyl) (CI-C alkyl) CI-C alkyl, CI-C 6 hydroxyalkyl, CI-C dihydroxyalkyl, CI-C 6 alkoxy CI-C 6 alkyl, -SO 2 (CI-C 6 alkyl), -S0 2 NH 2, -SO 2 NH(C!-C 6 alkyl) , -SO 2 N(CI-C 6 alkyl) (CI-C 6 alkyl) , or C -C 6 alkanoyl, each of which is optionally substituted with I, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF or OCF 3 . In this embodiment, it is preferred that at least one of ZI, Z 2 , and Z 3 is not hydrogen. Embodiment 31. Compounds according to embodiment 30, wherein Rs is of the formula: ZI z wherein Z 1 is H, halogen, CI-C 4 alkyl, CI-C haloalkyl, C -C hydroxyalkyl, C -C dihydroxyalkyl, or C -C alkoxy; and NR 6 R 7 (CI-C 6 aiky! ) , C! -C hydroxya!ky!, C- -CE dihydroxya!kyl, halogen, C 1 -C 4 a!koxy, CO=R, OH, C: -C 6 alkoxycarbonyl, or C -C haloalky!; Z 3 is H, C;-Q alkyl, -C (O) NR 6 RT, -(C -C alkvl)-C(O)NR 6 RT. -N-R R NR R (CI-CG alkyl) , C 1 -C hydroxyalkyi, C - C 6 dihydroxyalkyl, halogen, C!-C 4 alkoxy, CO 2 R, OH, C 1 -C 6 a!koxycarbonyl, or CI-C 4 haloaikyl, and wherein R 6 and R at each occurrence are independently H, OH, CI-C alkyl, amino CI-C 4 alkyl, NH(C 1 -C 6 alkyl)a!kyl, N(C 1 - C 6 alkyl)(Ci-C 6 a!kyl) C 1 -C alkyl, C- -C hydroxyalkyl, Ci-C 6 dihydroxya i kyl, CI-CG a! koxy Ci -C 6 alkyl, SO= (Ci-C 6 alkyl) , -S0 2 NH 2 , -S0 2 NH (Ci-C 6 alkyl) , - S0 2 N (C 1 -C 6 alkyl) (C 1 -C alkyi) , or C 1 -C 6 alkanoyl, each of which is optionally substituted with I, 2, or 3 groups that are independently halogen, OH, SH, C 3-CG cycloalkyl, CI-C 4 a!koxy, CI-C 4 alkyl, OH, CF or OCF In this embodiment, it is preferred that at least one of ZI, Z 2 , and Z is not hydrogen. Embodiment 32. Compounds according to embodiment 30, wherein Rs is of the formula: 7 1 Z 2 wherein Z 1 is H, halogen, CI-C 4 alkyl, C 1 -C 4 haloalkyl, Ci-C hydroxyalkyl, CI-C 4 dihydroxyalkyl, or CI-C 4 alkoxy; and Z 2 is CI-C 4 alkyl, -C(O)NR RT, -(C -C alkyl)-C(O)NR Rv, -NR Rv, NR R (C - C alkyl ) , C -C hydroxyalkyl, C -C dihydroxyalkyl, halogen, C -C alkoxy, CO 2 R, OH, C -C alkoxycarbonyl, or C -C haloa!kyl; H, CI-C 4 alkyl, -C(O)NR 6 R -(CI-C 4 aikyi)-C(O)NR 6 R -NR 6 R NR R (Cz - C 6 a i kyl ) , CI - C 6 hyd roxya I k¥1, CI - C 6 dihydroxyalkyl, halogen, CI-C 4 alkoxy, CO,R, OH, CI-C alkoxycarbonyl, or Cz-C 4 haloalkyl, and wherein R 6 and R at each occurrence are independently H, OH, Cz-C alkyl, amino CI-C alky!, NH(Cz-C a!kyl)alkyl, N(CzC alkyl)(CI-C 6 alkyl) CI-C 6 alkyl, CI-C hydroxyalkyl, Cz-C 6 dihydroxyalkyl, CI-C a ! koxy CI -C 6 al kyl, - SO 2 (Cz-C 6 a!kyl) , -SO 2 NH;, -SO 2 NH (Cz-C 6 alkyl) , -SO 2 N (CI-C 6 alkyl) (CzCG alkyl) , or Cz-C alkanoyl, each of which is optionally substituted with I, 2, or 3 groups that are independently halogen, OH, SH, C 3-C cycloalkvl, Cz-C 4 alkory, CI-C 4 alkyl, OH, CF 3 , or OCF 3 . In this embodiment, it is preferred that at least one of 2 , and Z 3 is not hydrogen. Embodiment 33. Compounds according wherein either 7 1 Z 1 "/ --Z 3 or Z 2 Z 2 , or Z 3 wherein is H, halogen, CI-C 4 alkyl, hydroxyalkyl, CI-C 4 dihydroxyalkyl, Cz-C 4 alkyl, -C(O)NR R - (CI-C 4 NR 6 R 7 ( C l - C a ikyl ) , C: - C dihydroxyalkyl, halogen, CI-C to embodiment 29, Z 1 or Z 2 Z 3 CI-C 4 haloalkyl, Cz-C 4 or C -C 4 alkoxy; and alkyl)-C(O)NE 6 RT. -NR 6 RT, hydroxya i kyl, Cz - C alkoxy, CO 2 R, Cm-CG a!koxycarbony!, - (CI-C 4 alkyl ) -NR!sC (0) NRI R! 7 , or - (CI -C alkyl ) -NR sC (0) R 18 ; H, Ci-C 4 alkyl, -C (O) NR RT, -(C:-C 4 aikyZ)-C(O)NR RT. -NR 6 RT, NR 6 R 7 (Ci-C 6 alkyl) , Ci-C 6 hydroxya!kyl , C--C dihydroxyalkyl, halogen, C -C alkoxy, CO,R, C!-C 6 alkoxycarbony!, - (C!-C 4 alkyl-NR!sC (O) NRI 6 R 17 , or - (CI-C a!kyl) -NRIsC (O) RiB; R 6, RT, and the nitrogen to which they are attached form a piperidinyl, pyrrolidiny!, pipera zinyl, or a morpholinyl ring optionally substituted with ! or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalkyl, or halogen; R 1 s is H or CI-C 6 alkyl; R and R 17 are independently H or CI-C alkyl; or R 16 , R 1 v, and the nitrogen to which they are attached form a morpholinyl ring; and RIB is CI-C 6 alkyl optionally substituted with -O- (C 2 -C 6 alkanoyl, CI-C hydroxyal kyl, CI-C 6 dihydroxyalkyl, C -C 6 alkoxy, CI-C 6 alkoxy C -C 6 alkyl; amino CI-C alkyl, mono or dialkylamino CI-C 6 alkyl. In this embodiment, it is preferred that at least one of 2 , and Z is not hydrogen. Embodiment 34. Compounds according to embodiment 33, wherein of the formula: 7 2 Z 3 is H, halogen, C -C 4 alkyl, C -C 4 haloalkyl, Ci-C 4 hydroxyalkyl, CI-C 4 dihydroxyalkyl, or Ci-C 4 alkoxy; and NR R (CI-C 6 alkyl ) , C:-C hydroxyalkyl, C 1 -C dihydroxyalkyl, halogen, Ci-C 4 alkoxy, C0 2 R, Ci -C alkoxycarbonyl, - (C:-C 4 a!kyl) -NRIsC (0) NR RI or - (Ci-C alkyl) -NRIsC (O)R 1 s; Z 3 is H, CI-C 4 alkyl, -C(O)NR RT, -(CI-C 4 alky!)-C(O)NR 6 RT.-NR 6 RT, NR R (Ci-C 6 alkyl) , C 1 -C hydroxyalkyl, C -C dihydroxyalkyl, halogen, CI-C 4 alkoxy, C0 2 R, C -C alkoxycarbonyl, - (C!-C 4 alkyl) -NRIsC (0) NRI 6 RI or - (CIC alkyl) -NRIsC (O) R 18 ; R 6, Rv, and the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, piperazinyl, or a morpholinyl ring optionally substituted with 1 or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalkyl, or halogen; R 1 is H or CI-C alkyl; R 16 and RI are independently H or CI-C 6 alkyl; or R 16, R 1 v, and the nitrogen to which they are attached form a morpholinyl ring; and R 18 is CI-C 6 alkyl optionally substituted with -0- (C 2 -C 6 al kanoyl, C 1 -C 6 hydroxyl kyl, CI -C 6 dihydroxyal kyl, CI-C 6 alkoxy, C -C alkoxy C -C alkyl; amino C -C alkyl, mono or dialkylamino C -C alkyl. In this embodiment, it is preferred hat at least one of Z Z and Z is not hydrogen. Embodiment 35. Compounds according to embodiment 33, wherein Rs is of the formula: 7 1 Z wherein is H, halogen, CI-C 4 alky! Ci-C 4 ha!oa!kyl, C!-C hydroxyalkyl, CI-C dihydroxyalkyl, or C:-C a!koxy; and C 1 -C 4 aikyl, -C (O) NR 6 R - (CI-C 4 aiky!)-C(O)h-R R 7 -NR 6 R NR R (CI-C 6 a!kyl) , CI-C hydroxyaikyi, C!-C 6 dihydroxyalky!, halogen, CI-C 4 a!koxy, CO,R, CI-C a!koxycarbonyl, - (C 1 -C alkyl)-NRIsC(O)NRI 6 R 17 , or - (C:-C 4 alkyl) -NRIsC (0) R 18 ; H, Ci-C 4 a!ky!, -C(O)NR 6 R -(C -C 4 alkyl)-C(O)NR RT. -NR 6 RT, NR 6 R (Ci-C 6 alkyl) , C -C 6 hydroxyalkyl, C:- C 6 dihydroxya!kyl, halogen, C -C 4 alkoxy, CO,R, C 1 -C a!koxycarbonyl, - (CI-C 4 alkyl) -hrR C (0) NRI 6 R 17 , or - (CI-C 4 alky!) -NR sC (0) R! 8 ; R 6, RT, and the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, piperazinyl, or a morphoi inyl ring, each of which is optionally substituted with 1 or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalkyl, or halogen; R 1 s is H or CI-C a!kyl; R 16 and R 1 v are independently H or CI-C 6 alkyl; or RI R 7 , and the nitrogen to which they are attached form a morpholinyl ring; and R 18 is CI-C alkyl optionally substituted with -0- (C 2 -C alkanoyl, C -C hydroxyalkyl, C -C dihydroxyalkyl, C -C alkoxy, C -C alkoxy C -C alkyl; amino C -C alkyl, mono or dialkylamino C -C alkyl. In this embodiment, it is preferred that at least one of Z and Z 3 is not hydrogen. Embodiment 36. A compound of the formula mharmaceutical!y acceptable salt thereof, wherein and M are indepedently selected from -0-, -CH 2 -, -S-,-kqg-, - N(R)-N(R)-, C(=O)-, -S0 2 -; Xe Xa Xe Xb Xd Xc or Xc , wherein 2 , Xa, Xb, Xc, Xd, and X, at are independently selected from -C (0) NR 6 RT, - (CI-C 4 alkyl) -C (O) NR 6 R -NR 6 R hydroxy (C 1 - C 4)alkyl, CI-C 4 dihydroxyalkyl, H, OH, halogen, haloalkyl, alkyl, haloalkoxy, heteroaryl, heterocycloaikyl, C] -C cycloalkyl, R 6 R N- (C 1 -C 6 alkyl) -, -CO 2 - (Ci-C 6 ) alkyl, -N(R)C(O)NR RT, -N(R) C(O)-(C 1 -C 6 )alkoxy, C0 2 R- (CI-C 6 alkyl)- , or - SO 2 NR 6 R ; wherein the het eroaryl and heterocycloalkyl groups are optionally substituted with - NR 6 Rv, -C(O)NR R R RvN- (CI-C alkyl)-, CI-C 6 alkyl, CI-C alkoxy, or halogen; or heteroaryl or heteroarylalkyl, wherein the heteroaryl and heteroaryl groups are optionally substituted with 1,2, 3, or 4 groups that are independently -C (O) NR 6 Rv, - (CI-C 4 alkyl ) -C (O) NRGRT, -NR 6 R hydroxy (CI-C 4 ) alkyl, Ci-C 4 dihydroxyalkyl, H, OH, halogen, haloalkyl, alkyl, haloalkoxy, R 6 RTN- (CI-C 6 alkyl) -, -CO 2 - (CI-C ) alkyl, -N(R) C(O)NR 6 RT, or -N(R)C(O)- (Ci-C 6 )alkoxy; wherein R and Rv are independently at each occurrence H, CI-C 6 alkyl, CI-C 6 alkoxy, CI-CG alkoxy CI-C 6 alkyl, CI-C alkoxycarbonyl, OH, CI-C 6 hydroxyalkyl, CI-C 4 dihydroxyalkyl, CI-C 6 thiohydroxyalkyi, - (C 1 -C 4 )a!ky!- C0 2-alkyl, pyridyl Ci-C 6 alkyl, C -C alkanoyl, benzyl, phenyl C!-C 6 alkoxy, or pheny! C=-C 6 alkanoyi, wherein each of the above is unsubst inured or substituted with 1, 2, or 3 groups that are independently, halogen, C 3 -C cycloa!kyl, C:-C alkoxy, piperidiny! C:-C 6 alky!, morphoi iny! C,-C 6 alky!, piperazinyl Ci-C 6 alky!, OH, SH NH 2 , NH(alkyl), N(alkyl) (alkyl), -O-C -C aikanoyl C 1 -C alkyl, CF 3 , or OCF 3 ; or Re, Rv, and the nitrogen to which they are attached form a morphol inyl, thiomorphol inyl, piperidinyl, pyrrol idinyl, or piperazinyl ring which is optionally substituted with I or 2 groups that are independently CI-C 4 alkyl, Ci-C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, C=-C 4 dihydroxyalkyl, or halogen; R at each occurrence is independently H or CI-C alkyl; Y Y 2 , Y and Y 4 are independently selected from H, halogen, alkyl, carboxaldehyde, hydroxyalkyl, dihydroxyalkyl, alkenyl, alkynyl, CN, alkanoyl, alkoxy, alkoxyalkyl, haloalkyl, and carboxyl. Embodiment 37. Compounds according to embodiment 36 of the formula H Y X 2 " 1 Y 2 XI" "N "O R pharmaceutically acceptable salt thereof. Embodiment 38. Compounds according to embodiment wherein Xe Xb Xd Xc Rs is Xc or embodiment Embodiment 39. Compounds according to wherein Y 2, Y 4 , and Y are independently halogen; and Y: and Y 3 are both hydrogen. Embodiment 40. Compounds according to embodiment wherein Xa X0 Xb // Xd Rs i s Xc ; XI and X 2 are independently H, methyl, NR 6 Rv, - (Ci-C 4 alkyl)- C(O)NR 6 R RGRTN- (C 1 -C alkyl) -,-C (O) NR 6 RT, or - (CI-C 4 alkyl) hydroxyalkyl, C 1 -C dihydroxyalkyl, morpholinyl; and Xa and X are independently halogen, NH 2 , NH(CI-C alkyl), C 6 alkyl) (CI-C 6 alkyl), methyl, or hydrogen. In this embodiment, it is preferred that one of Xa and is not hydrogen. Embodiment 41. Compounds according to embodiment whe re in one of Xb and Xc is hydrogen and the other is -NR 6 RT, R 6 RvN-(CIC 6 alkyl)-, -C (O) NR 6 RT, -SO 2 NR 6 Rv, or halogen; where R 6 and R are independently at each occurrence H, CI-C alkyl, C 1 -C alkoxy, C:-C a!koxy CI-C 6 alkyl, C:-C 6 ai koxycarbonyl OH, C: - C hydroxya i kyi, C - C dihydroxya!kyl, - (C=-C )aikyl-CO -alkyi, pyri=yl CI-C 6 alkyl, C:-C aikanoy!, benzyl, phenyi C-~C 6 alkex¥, or pheny! C 1 -Ce a!kanoy!, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, C 3 -C 6 cycloa!kyl, CI-C 6 alkoxy, piperidinyl C 1 -Ce a!kyl, morpholinyl C 1 - Ce alky!, piperazinyl CI-C alkyl, OH, SH, NH 2 , NH(alkyl), N(alkyl) alkyl), -O-CI-C 4 alkanoyl, C!-C 4 alkyl, CF 3 , or OCF 3 ; or R 6, Rv, and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with ! or 2 groups that are independently CI-C alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 a!kyl, CI-C 4 dihydroxyalkyl, or halogen. Embodiment 42. Compounds according to embodiment 41, wherein Re and R 7 are independently at each occurrence H, CI-C 6 alkyl, CI-C alkoxy, CI-C alkoxy CI-C 6 alkyl, CI-C 6 alkoxycarbonyl, OH, CI-C 6 hydroxyalkyl, CI-C 6 dihydroxyalkyl, - (CI-C 4 ) alkyl-CO 2 -alkyl, pyridyl CI-C 6 alkyl, CI-C 6 alkanoyl, benzyl, phenyl CI-C alkoxy, or phenyl CI-C alkanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, C 3 -Ce cycloalkyl, CI-Ce alkoxy, piperidinyl CI-C alkyl, morphol inyl CI-C alkyl, piperazinyl CI-C 6 alkyl, OH, NH 2 , NH (alkyl) , N(alkyl) (alkyl) , -O-C -C 4 alkanoyl, CI-C 4 alkyl, CF 3 , or Embodiment 43. Compounds according to embodiment wherein Xa is hydrogen, methyl, fluorine, or chlorine; Xc and Xd are both hydrogen; Xb is -NR 6 RT, -(CI-C 4 alkyI)-C(O)NR R R R N-(C -C 6 alkyl)-, C(O)NR 6 R ; wherein R 6 and Rv are independently at each occurrence H, C:-C 6 alkyl, C -C 6 hydroxyalkyl, CI-C 4 dihydroxyalkyl, CI-CG alkoxy, CG alkoxy CI-C 6 a!kyl, or CI-C alkanoyl, wherein each the above is optionally substituted with i, 2, or groups that are independently OH, SH, halogen, or C -CG cycloalkyl. Embodiment 44. Compounds according to embodiment wherein Xa, Xe Rs i s Xc ; Xa is H, fluoro, chloro, or methyl; Xe is hydrogen, halogen, or methyl; and Xb is H; Xd is H or halogen; Embodiment 45. Compounds according to embodiment wherein Xc is -SO 2 NRGRv, or halogen; wherein RG and Rv are independently at each occurrence H, CI-C alkyl, CI-C alkoxy, CI-C 6 alkoxy CI-C alkyl, CI-C alkoxycarbonyl, OH, CI-C 6 hydroxyalkyl, CI-C dihydroxyalkyl, - (Ci-C 4 )alkyl-CO 2 -alkyl, pyridyl CI-C alkyl, C:-C alkanoy!, benzyl, pheny] CI-C 6 alkoxy, or phenyl C:-C a!kanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, C 3 -C 6 cycloa!kyi, CI-C 6 alkoxy, piperidinyl C 1 -C alkyl, morpholinyl C!- C 6 alkyl, piperazinyl C=-C 6 aiky!, OH, SH, kq 2, NH(alkyl), N(alkyl) (alkyl), -O-CI-C 4 a!kanoy!, C 1 -C alkyl, CF or OCF 3 ; or RG, Rv, and the nitrogen to which they are attached form a morphol inyl, thiomorphol inyl, piperidinyl, pyrrolidiny!, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently Ci-C 4 alkyl, Ci-C 4 al koxy, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalkyl, or halogen; or Xc is fluoro, chloro, -N-H 2 , -NH(CI-C 6 alkyl , -N(CI-C 6 alkyl)(CIC 6 alkyl) , -SO 2 NH 2 , -SO 2 NH (C:-C 6 alkyl) , -SO=N (Q-C 6 alkyl) (CIC 6 alkyl) , or piperazlnyl, wherein the piperazinyl group is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalkyl, or halogen. Embodiment 46. Compounds according to embodiment 44, wherein Xc is -C(O)NR 6 RT, -(CI-C 6 alkyI)-C(O)NR 6 R -NR 6 R or R RvN- (CI-C 6 alkyl)-; wherein R 6 and Rv are independently at each occurrence H, CI-C 6 alkyl, C -CG alkoxy, CI-C 6 alkoxy CI-C 6 alkyl, CI-C alkoxycarbonyl, OH, CIC 6 hydroxyalkyl, Ci -C 6 dihydroxyalkyl, CI-C 6 dihydroxyal kyl, - (CIC 4 ) alkyl - C0 2alkyl, pyridyl CI -C 6 alkyl, CI-C 6 alkanoyl, benzyl, phenyl CI-CG alkoxy, or phenyl C 1 -C alkanoyl, unsubstituted or wherein each of the above is substituted with I, 2, or 3 groups that are cycloalky!, C:-C 6 independently, halogen, C 3 -C 6 morpholinvl C -C 6 alkoxy, piperidinyl CI-C alkyl, -NH 2, -NH(alkyl), a!kyl 0 piperazinyl CI-C alkyl, OH, -N(alky!) (alkyl), -0-Ci-C 4 alkanoy!, Ci-C 4 a!kyl, CF 3 , or OCF 3 ; or R R and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with ! or 2 groups that are independently CI-C 4 alkyl, C -C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalkyl, or halogen. Embodiment 47. Compounds according to embodiment 46, wherein Re is hydrogen; and R 7 is CI-C 6 alkyl or CI-C alkanoyl, each of which is optionally substituted with I, 2, or 3 groups that are independently NH 2, NH(C -C 6 alkyl), N(CI-C 6 alkyl) (CI-C 6 alkyl), OH, SH, cyclopropyl, or CI-C 4 alkoxy; to embodiment 47, Embodiment 48. Compounds according wherein Xc is -C(O)NR 6 R to embodiment 47, Embodiment 49. Compounds according where in Xc is NR 6 R or R 6 R N-(CI-C 6 alkyl)-. to embodiment 38, Embodiment 50. Compounds according wherein Xa is hydrogen; two of Xb, Xc, and Xd are hydrogen and the other is -C (O) NR R -(C 1-Ce a!kyl)-C(O)b'ReR -kTR 6 R=, R R N- (C 1 -Ce alky!)- or C0 2- (Ci-Ce)alky!; wherein Re and R 7 are independently at each occurrence H, C:-C 6 alkyl, CI-C 6 alkoxy, Ci-Ce alkoxy Ci-Ce alkyl, Ci-Ce al koxycarbonyl, OH, C 1 - Ce hydroxyalkyl, CI - Ce dihydroxya!kyl, - (Ci-C 4 )alkyl-C0 2 -alkyl, pyridyl CI-C 6 alkyl, CI-Ce alkanoyl, benzyl, phenyl CI-C 6 alkoxy, or phenyl CI-C 6 alkanoyl, wherein each of the above is unsubstituted or substlt'ated with i, 2, or 3 groups that are independently, halogen, C 3 -C 6 cycloalkyl, CI-C 6 alkoxy, piperidinyl CI-Ce alkyl, morpholinyl CICe alkyl, piperazinyl CI-Ce alkyl, OH, NH 2 , NH(alkyl), N(alkyl) (alkyl), -O-CI-C 4 alkanoyl, CI-C 4 alkyl, CF 3 , or OCF 3 ; or Re, RT, and the nitrogen to which they are attached form a morphol inyl, piperidinyl, pyrrol idinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, CIC 4 dihydroxyalkyl, or halogen ; and Xe is hydrogen, methyl, CI-C 2 alkoxy, or halogen. Embodiment 51. Compounds according to embodiment 50, wherein Xb is -C(O)NR 6 RT. -(CI-Ce alkyI)-C(O)NR 6 R -NRGRT, or ReRTN-(CI-C alkyl)- wherein Re is hydrogen or CI-C 4 alkyl; R 7 is OH, Ci-Ce alkyl or CI-C alkanoyl, wherein the alkyl and alkanoyl groups substituted with I, 2, or 3 groups that are independently 4 2 , NH(CI-Ce alkyl), N(CI-Ce alkyl) (CI-C alkyl), C 3 -Ce cycloalkyl, OH, or CI-C 4 alkoxy. Embodiment 52. Compounds according to embodiment 38, wherein Xa is halogen or methyl; Xb is H, -NR 6 RT, R 6 RTN- (C -C alkyl)-, -C(OINR 6 R or -CO 2 - (C:- C 6) alkyl ; Xc is -NR R R R N-(CI-C 6 alkyl)-, -C (O) NR 6 R halogen, -CO 2 -(C 1 - C 6)alkyl, NH 2 , NH(CI-C 6 alkyl), N(CI-C 6 alkyl)(CI-C 6 alkyl), - SO 2 NH 2 , -SO 2 NH (CI-C alkyl) , - SO 2 N(CI-C 6 alkyl) (CI-C 6 alkyl), or piperazinyl, wherein the piperazinyl group is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, CI-C 4 dihydroxyalkyl, or halogen; Xd is hydrogen; Xe is H, methyl, NH 2 , NH(CI-C 6 a!kyl) or N(CI-C 6 alkyl) (CI-C 6 alkyl ) . Embodiment 53. Compounds according to embodiment 38, wherein X 1, X 2 , Xa, Xb, Xc, Xd, and Xe are independently selected from H, OH, halogen, CF 3 , alkyl, OCF 3 , pyridyl, pyrida zinyl, pyrimidyl, pyrazinyl, thienyl, furyl, pyrrolyl, piperidinyl, piperazinyl, or C 3 -Cv cycloalkyl, wherein each of the above is optionally substituted with -NR Rv, -C(O)NR RT, - (CI-C 4 alkyl-C(O)NR6RT, 6 RT, R 6 R N- (CI-C 6 alkyl)-, CI-C 6 alkyl, CI-C alkoxy, or halogen. Embodiment 54. Compounds according to embodiment 37, wherein R 5 is a heteroaryl or heteroarylalkyl group, where each heteroaryl is pyrazolyl, imidazolyl, furanyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, imidazolyl, dihydroindolyl, dihydroisoindolyl, indolon-2yl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, dihydroi soquinol inyl, or indoly!, each of which is optionally substituted with i, 2, 3, or 4 groups that are independent !y -C (O) Nervous, - C!-C 4 alkyl)-C(O)hIR 6 R -NR 6 R hydroxy (C:-C 4 ) alky!, C:-C 4 dihydroxyalkyl, hydrogen, hydroxy, halogen, haloalkyl, alkyl, haloalkoxy, R 6 RTN- (CIC 6 alkyl)-, -C0 2 - (Ci-C 6 )alkyl, -N(R) C(O)NR RT, or -N(R)C(O)- (Ci-C 6 )alkoxy; wherein R 6 and R 7 are independently at each occurrence H, CI-C alkyl, CI-C 6 alkoxy, CI-C 6 alkoxy C!-C 6 alkyl, CI-C 6 alkoxycarbonyl, OH, CI-C hydroxya! kyl, CI - C dihydroxyalkyl, C:-C thiohydroxyalkyl, - (CI-C 4 )alkyICO 2alkyl, pyridyl CI-C 6 alkyl, CI-C 6 alkanoyl, benzyl, phenyl CI-C 6 alkoxy, or phenyl C:-C 6 alkanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, C 3 -C 6 cycloalkyl, CI-C alkoxy, piperidinyl C -C 6 alkyl, morpholinyl C -C alkyl, piperazinyl C -C 6 alkyl, OH, SH, N-H 2 , NH(alkyl), N(alkyl) (alkyl), -O-CI-C 4 alkanoyl, CI-C 4 alkyl, CF 3 , or OCF Embodiment 55. Compounds according to embodiment 54, wherein Y 2, Y 4 , and Y are independently halogen; and YI and Y 3 are both hydrogen. Embodiment 56. Compounds according to embodiment 55, wherein X and X 2 are independently H, methyl, -NR 6 R R 6 R N- (CI-C alkyl) -, -C (O) NR R - (CI-C 4 alkyl) -C (O) NR 6 RT, CI-C hydroxyalkyl, CI-C dihydroxyalkyl, or - (CI-C alkyl)-morpholinyl. Embodiment 57. Compounds according to embodiment 56, wherein Rs is pyridyl Ci-C 6 alkyl, pyrimidinyl C!-C a!kyl, or pyrazinyl C -C 6 alkyl, each of which is optionally substituted with i, 2, or 3 groups that are independently hydroxy(C 1 - C 4)alkyl, CI-C 4 dihydroxyalkyl, OH, halogen, CF 3 , (C-- C 4)alkyl, OCF 3 , -NRGRT, - (CI-C 4 alk¥1) -C(O)NR 6 RT, R 6 RTN- (CIC 6 alkyl-, or -C (O) NR R Embodiment 58. Compounds according to embodiment 57, wherein Rs is of the formula: wherein Zs is hydroxy(Ci-C 4 )alkyl, CI-C 4 dihydroxyalkyl, OH, halogen, CF 3, (Ci-C 4 )alkyl, OCF 3 , -NR 6 RT, R 6 R N- (CI-C 6 alkyl)-, -(CIC 4 alkyI)-C(O)NR 6 R or-C(O)NR RT, wherein R 6 and Rv at each occurrence are independently H, CI-C 6 alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C -C 6 cycloalkyl, OH, SH, or CI-C 4 alkoxy. Embodiment 59. Compounds according to embodiment 57, wherein R 5 is of the formula: "5 wherein Zs is hydroxy(Ci-C 4 )alkyl, CI-C 4 dihydroxyalkyl, OH, halogen, CF 3, (CI-C 4 )alkyl, OCF 3 , -NR Rv, R RvN- (CI-C alkyl)-, - (CIC 4 alky1)-C(O)NR 6 RT, or-C(O)NR Rv, wherein R 6 and R at each occurrence are independen=!y H, C:-C alkyl optionally substituted with I, 2, or 3 groups that are independently CI-C 4 a!koxycarbonyl, halogen, C 3-C cycloalkyl, OH, SH, or CI-C 4 a!koxy. Embodiment 60. Compounds according to embodiment 57, wherein N N// Z 20, wherein R is of the formula: Z 0 is H or methyl; and Z 20 is - (Ci-C 4 alkyl) -C (O) NR 6 RT, hydroxy (Ci-C 4 ) alkyl, Ci-C 4 dihydroxyalkyl, OH, halogen, CF 3 , (CI-C 4 ) alkyl, OCF -NR 6 Rv, R 6 RTN-(CI-C 6 alkyl)-, or-C(O)NR 6 R , wherein R 6 and R 7 at each occurrence are independently H, CI-C 6 alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-C 6 cycloalkyl, OH, SH, or C -C 4 alkoxy. Embodiment 61. Compounds according to embodiment 57, wherein Z Rs is of the formula: Z20, wherein Z 10 is H or methyl; and Z 20 is - (CI-C 4 alkyI)-C(O)NR 6 RT, hydroxy(Ci-C 4 )alkyl, CI-C 4 dihydroxyalkyl, OH, halogen, CF (CI-C 4 ) alkyl, OCF 3 , -NR 6 R R RTN-(CI-C alkyl)-, or-C(O)NR 6 RT, wherein R 6 and Rv at each occurrence are independently H, CI-C alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-C 6 cycloalkyl, OH, SH, or C -C 4 alkoxy. Embodiment 62. Compounds according to embodiment 57, wherein I \N " Z 20 wherein Rs is of the formula: Z 10 is H or methyl; and Z 20 is - (CI-C 4 alkyl) -C(O)NR 6 Rv, hydroxy(Ci-C 4 )alky!, C!-C dihydroxyalkyl, OH, halogen, CF (C -C 4 ) alkyi, OCF 3 , -NR RT, R R N-(CI-C 6 alkyl)-, or-C(O)NR 6 R , wherein R and R 7 at each occurrence are independently H, CI-C 6 alkyl optionally substituted with !, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-C 6 cycloalkyl, OH, SH, or CI-C 4 alkoxy. Embodiment 63. Compounds according to embodiment 57, wherein Z Rs is of the formula: Z20, wherein Z 10 is H or methyl; and Z 20 is - (CI-C 4 alkyI)-C(O)NR RT, hydroxy(Ci-C 4 )alkyl, CI-C 4 dihydroxyal kyl, OH, halogen, CF 3 , ( CI - C 4 ) alkyl, OCF 3 , -NR 6 RT, R R N-(CI-C alkyl)-, or-C(O)NR Rv, wherein R and R 7 at each occurrence are independently H, Ci-Cs alkyl optionally substituted with I, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-C 6 cycloalkyl, OH, SH, or CI-C 4 alkoxy. Embodiment 64. Compounds according to embodiment 57, wherein <2. Rs is of the formula: Z20, wherein Z:c is H or methyl; and Z 20 is - (C 1 -C alky!)-C(O)NR 6 Rv, hydroxy(C:-C )aikyl, C:-C dihydroxyalky!, OH, halogen, CF 3 , (C - C 4 ) alkyl, OCF 3 , -NR 6 R?, R 6 R N- (CI-C 6 alkyl) -, or -C (O) MR 6 R wherein R 6 and Rv at each occurrence are independently H, CI-C 6 a!kyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-C cycloalkyl, OH, SH, or C -C 4 alkoxy. Embodiment 65. Compounds according to embodiment 57, wherein Rs is of the formula: Z2o, wherein Z 10 is H or methyl; and Z 20 is -(CI-C 4 alkyII-C(O)NRGRT, hydroxy(Ci-C 4 )alkyl, CI-C 4 dihydroxyalkyl, OH, halogen, CF 3 , (C:-C 4 ] alkyl, OCF 3 , -NR 6 R 7, R 6 RTN- (CI-C 6 alkyl)-, or -C(O)NR R wherein R 6 and R? at each occurrence are independently H, CI-C 6 alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, Cs-C cycloalkyl, OH, SH, or CI-C 4 alkoxy. Embodiment 66. Compounds according to embodiment 57, wherein Z /N Z 20 , R 5 is of the formula: wherein Z 10 is H or methyl; and Z 20 is - (C 1 -C 4 alkyI)-C(O)NR R hydroxy(C:-C 4 )a!kyl, C 1 -C dihydroxya!kyl, OH, halogen, CF 3 , (CI-C 4 ) alkyl, OCF 3 , -NR 6 Rv, R 6 R N-(Q-C alkyl)-, or-C(O)NR 6 Rv, wherein Re and R 7 at each occurrence are independently H, CI-C 6 alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C -CG cycloalkyl, OH, SH, or CI-C 4 alkoxy. Embodiment 67. Compounds according to embodiment 57, wherein Z Rs is of the formula: Z2o, wherein Z 10 is H or methyl; and Z 20 is - (CI-C 4 alkyl-C(O)NR6Rv, 6 Rv, hydroxy(Cz-C 4 )alkyl, C -C 4 dihydroxyalkyl, OH, halogen, CF 3 , (CI-C 4 ) alkyl, OCF 3 , -NR RT, R 6 RvN-(CI-C alkyl)-, or-C(O)NR RT, wherein Re and R at each occurrence are independently H, CI-C alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-CG cycloalkyl, OH, SH, or CI-C 4 alkoxy. Embodiment A7. Compounds according to embodiment 1 wherein is H, halogen, alkyl optionally substituted with CI-C 4 alkoxycarbonyl, C 2 -C alkenyl optionally substituted with CI-C 4 alkoxycarbonyl, C 2 -C 4 alkynyl, CI-C 4 haloalkyl, carboxaldehyde, CI-C 4 hydroxyalkyl, phenyl(Cz-C )alkoxy, benzyl, phenethyl, phenpropyl, CN, or phenyl(C - wherein the phenyl groups are unsubst itut ed or subst ituted with !, 2, or 3 groups that are independently halogen, CI-C aikyl, C!-C 4 a!koxy, nitro, CN, CF 3 , OCF 3 or CO,H; is OH, benzyloxy, phenyloxy, (C -C 4) thioalkoxy, -OC(O)N(aikyl) (CH 2 )nphenyl, pheny!oxy(C -C )alky!, phenyl -OC (O) NZ4 (CH 2 ) nphenyl, di(C 1 -C 6 )alkylamino, C=-C a!kynyl, pyridyl, pyrimidyl, pyridazyl, pyrazo!yl, imidazolyl, pyrrolyl, tet rahydroquinol inyl, tetrahydroisoquinolinyl, tetrazolyl, pyrazinyl, benzimidazolyl, triazinyl, tetrahydrofuryl, piperidinyl, hexahydropyrimidinyl, thiazolyl, thienyl, or CO 2 H, wherein n is 0, i, 2, 3, 4, 5 or 6; each of the above is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently halogen, NR 6 R (C 1 -C 4 ) haloalkyl, (Ci-C 4 ) haloalkoxy, (Ci-C 6 ) alkyl, pyridy!, - (CI-C 6 ) alkyl-N (R) -CO 2 R 0 , or NR 6 R - (C 1-C 6 alkyl)-, H, alkyl optionally substituted with one or two groups that are independently CO 2 H, -C0 2 alkyl, -C(O)NRR, - N(R 30)C(O)NRR, -N(R 30 )C(O)- (C 1 -C 6 )alkoxy, or -NR 6 Rv, phenyl (C 1 -CG) alkoxy, phenyl (C 1 -C 6 ) alkyl, hydroxyalkyl, wherein the phenyl groups are unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, CF 3 , or OCF ; and phenyl(Q-C )alkyl, (C 1 -C )alkyl, phenyl, piperidinyl(C 1 - C ) alkyl, thienyl (CI-C ) alkyl, indolyl, quinolinyl, isoquinolinyl, isoindolyl, indol2-onyl, indazolyl, indolyl (Ci-C 6 ) alkyl, quinolinyl (Ci-C 6 ) alkyl, isoquinolinyl(C 1-C ) alkyl, is 0 indolyl(C 1 -CG) alkyl, indol2-onyl (CI-C 6 ) alkyl, naphthyl (C 1 -C ) alkyl, pyridyl (CiC )alkyl, pyrimidy!(C 1 -C 6 )alkyl, pyrazinyl(C 1 -C )a!ky!, or wherein each of the above is unsubstituted or substituted with !, 2, 3, 4, or 5 groups that are independently alkyl, halogen, a!koxy, benzyloxy, thioalkoxy, -C0 2 (CI-Cs alkyl) , C0 2 H, CN, amidinooxime, NRsRg, krR 6 R - (CI-C 6 alkyl)-, -C(O)NR 6 R amidino, CF 3 , or OCF 3 ; R 8 is hydrogen, C 1 -C 6 alkyl, CI-C 6 alkanoyl, phenyl C 1-C alkyl and phenyl CI-C 6 alkanoyl; and R 9 is aminoalky!, mono CI-C 6 alkylamino C 1 -C 6 a!kyl, di CIC 6 alkylamino CI-C 6 alkyl, C 1 -C alkyl, C 1 -C alkanoyl, phenyl Ci-C 4 alkyl, indazolyl, and phenyl Ci-C 4 alkanoyl. In this embodiment, it is preferred that when R 2 is benzyloxy, R 4 is H, and Rs is benzyl or methyl, RI is not hydrogen; and no more than two of RI, R 2 , R 4 , and Rs are simultaneously hydrogen. Embodiment AS. Compounds according to embodiment A7 wherein RI is H, halogen, CI-C 4 alkyl optionally substituted with CI-C 4 alkoxycarbonyl, C 2 -C 4 alkenyl optionally substituted with CI-C 4 alkoxycarbonyl, C 2 -C 4 alkynyl, or carboxaldehyde; R 2 is benzyloxy, OH, phenyloxy, phenyloxy(Ci-C 6 ) alkyl, phenyl (C -C 4) thioalkoxy, or pyridyl; wherein each of the above is optionally substituted with i, 2, 3, 4, or 5 groups that are independently halogen, - (CI-C 6 )alkyI-N(R)-CO 2 R 30 , NR RT, (CI-C 4 ) haloalkyl, (CI-C 4 ) haloalkoxy, (CI-C 6 ) alkyl 0 pyridyl, or NR RT-(CI-C 6 alkyl)-. Embodiment Ag. Compounds according to embodiment A7 wherein R is H, (C -C )a!kyl optionally substituted with one or two groups that are independently C0 2 H, -CO 2 alky!, -C(O)NRR, -N(R 30)C(O)NRR, -N(R 0 )C(O)- (C 1 (Co-C )alkoxy, or -N'R 6 RT, phenyi(C 1-C 6)alkoxy, or hydroxy(C 1 -C 6 )alkyl, wherein the phenyl groups are unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, hydroxy, CI-C alkoxy, C!-C 4 alkyl, nitro, CF 3 , OCF ; and Rs is benzy!, phenethyl, phenpropyl, phe butyl, (C 1 -C )a!kyl, phenyl, pyridyl, pyrimidy!, indolyl, indazolyl, indolyl (C!-C 6) alkyi, naphthy! (CI-C 6 ) alkyl, thienyl (CI-C 6 ) alkyl, pyridyl (C 1 -C 6 ) alkyl, pyrimidyl (C 1 -C 6 ) alkyl, or pyrazinyl(C 1-C 6)alkyl, and wherein each of the above is unsttbstituted or substituted with I, 2, or 3 groups that are independently alkyl, halogen, alkoxy, benzyloxy, thioalkoxy, -CO 2 (CiCs alkyl) , CF 3 , OCF CO 2 H, CN, amidinooxime. In this embodiment, it is preferred that when R 2 is benzyloxy, R 4 is H, and Rs is benzyl or methyl, RI is not hydrogen; and no more than two of RI, R 2 , R 4 , and Rs are simultaneously hydrogen. Embodiment AI0. Compounds according to embodiment A7, wherein R 4 is H, (CI-C 4 ) alkyl optionally substituted with one or two groups that are independently C0 2 H, -CO 2 alkyl, -C(O)NRR, -N(R 30) C (0) NRR, -N (R 30 )C (0)- (CI-C 6 )alkoxy, or -NR 6 Rv, phenyl (CI-C 6 ) alkoxy, benzyl, phenethyl, phenpropyl, or hydroxy(Ci-C )alkyl, wherein the phenyl groups are unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, hydroxy, CI-C alkoxy, C 1 -C alkyl, nitro, CF 3 , OCF 3 ; and indolyl, quinolinyl, isoquino!inyl, isoindo!y!, indol-2ony!, indoly! (CI-C 6 ) alkyl, quino!inyl (C -C ) alkyl, isoquinolinyl(CI-C ) alkyl, is 0 ind 0 lyl(Ci-C 6 ) alky!, indol2-onyl (CI-C 6 ) alkyl, each of which is unsubstituted or substituted with I, 2, or 3 groups that are independently C -C 4 alkyl, halogen, CF 3 , OCF 3 , -CO 2 CH 3 , CI-C 4 hydroxya!kyi, CI-C 4 alkoxy, -CO 2 (C:-Cs alkyl) , benzyloxy, NRsRs, NR RT- (CI-C alkyl) -, -C (O) NEGRO or amidinooxime ; wherein R 6 and R are independently at each occurrence H, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, alkanoyl, phenylalky!, phenylalkoxy, or phenylalkanoyl, wherein each is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, hydroxy, C -C 4 alkoxy, OH, SH, C 3 -C cycloalkyl, CI-C 4 alkyl, CF 3 , or OCF 3 ; or R and the nitrogen to which they are attached form a m 0 rpholinyl 0 thiomorpholinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy C -C alkyl, or halogen. Compounds according to embodiment A7 Embodiment All. wherein is chloro, bromo, iodo, or H; and quinolinyl, is benzyl, phenethyl, phenpropyl, phenyl, indol-2-onyl, indolyl, isoquinoliny!, isoindolyl, indolyl (CI-C ) alkyl, quinolinyl (CI-C 6 ) alkyl, is 0 quin 0 linyl(C 1-C 6) alkyl, isoindolyl(Ci-CG) alkyl, indol2-onyl(Ci-C ) alkyl, piperidinyl CI-C 4 alkyl, thienyl CI-C alkyl, - CH 2 - pyr idy I, or pyridyl, each of which is unsubstituted or substituted with i 2, or 3 groups that are independently C!-C a!ky!, halogen, CF 3 , OCF 3 , CI-C 4 hydroxyalkyl, C=-C 4 aikoxy, -CO 2 (C -Cs alkyl, benzyloxy, NRsRg, NR 6 R 7 C -C 4 alkyl, - C (0) 6 R and amidinooxime ; wherein R 6 and R 7 are independently at each occurrence H, alkyl, hydroxya!kyl, alkoxy, alkoxya!kyl, alkanoyl, phenylalkyl, phenyla!koxy, or pheny!alkanoyl, wherein each is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, hydroxy, CI-C 4 alkoxy, OH, SH, C 3 -C 6 cycloalky!, CI-C 4 alkyl, CF 3 , or OCF ; or R R and the nitrogen to which they are attached form a morpholinyl, thiomorpholiny!, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently C -C a!kyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment AI2. Compounds according to embodiment wherein benzyl, phenethyl, phenpropyl, or phenyl, each of which is unsubstituted or substituted with I, 2, or 3 groups that are independently CI-C 4 alkyl, halogen, CF OCF - CO CH 3, CI-C 4 hydroxyalkyl, CI-C 4 alkoxy, -CO 2 (CI-Cs alkyl), benzyloxy, NRsRg, NR 6 R Ci-C 4 alkyl, -C (O) NR R 7 , and amidinooxime. Embodiment AI3. Compounds according to embodiment wherein quinolinyl, indolyl, isoquinolinyl, isoindolyl, indol-2onyl, indolyl (Q-C 6 ) alkyl, quinolinyl (CI-C ) alkyl, isoquinolinyl(Ci-C 6) alkyl, isoindolyl (CI-C 6 ) alkyl, indol2-onyI(C -C 6) alkyl, piperidinyl CI-C 4 alky], thienyl CI-C 4 alkyl, - CH 2 -pyridyl, or pyridyl, each of which is unsubstituted or substituted with i, 2, or 3 groups that are independently CI-C a!kyl, halogen, CF 3 , 0C? 3 , -C0 2 CH 3 , CI-C 4 hydroxya!kyl, CI-C 4 alkoxy, -CO 2 (C:-Cs alkyl) , benzyloxy, NRsR NR R C!-C alkyl, -C (O) NrR R=, and amidinooxime. Embodiment AI4. Compounds according to any one of embodiments All, AI2, or A!3 wherein R 2 is benzyloxy, or phenethyloxy; each of the above is unsubstituted or substituted with i, 2, or 3, groups that are independently -(CI-C 6 )alkyI-N(R)- CO 2 R 30, fluoro, chloro, bromo, CF 3 , or (Ci-C 4 )alkyl. Embodiment AI5. Compounds according to any one of embodiments All, AI2 or AI3 wherein R 2 is phenyloxy (CIC 6 ) alkyl, wherein the phenyl group is unsubstituted or substituted with i, 2, or 3, groups that are independently - (CI-C 6 ) alkyl-N(R) -CO 2 R 30 , fluoro, chloro, bromo, CF], or (Ci-C 4 )alkyl. Embodiment AI6. Compounds according to embodiment AI, wherein R 1 is H, halogen, CI-C 4 alkyl optionally substituted with CI-C 4 alkoxycarbonyl, C 2 -C 4 alkenyl optionally substituted with CI-C 4 alkoxycarbonyl, C 2 -C 4 alkynyl, or carboxaldehyde. Embodiment AI7. Compounds according to embodiment AI6, wherein R 2 is benzyloxy, OH, phenyloxy, phenyloxy (CI-C 6 ) alkyl, or phenyl (CI-C 4 ) thioalkoxy, wherein each of the above is optionally substituted with i, 2, 3, 4, or 5 groups that are independently halogen, - (CI-C 6 )alkyI-N(R)-CO 2 R 30 , NR 6 RT, (Ci-C 4) haloa!kyl, (C!-C ) ha!oalkoxy,(e 1-c 6) aikyl, pyridy3, or NR R - (Cz-C a!kyl)-. Embodiment AIS. Compounds according to embodiment AfT, wherein R is H, or (CI-C ) aiky! optionally subs=i u ed with one or two groups that are independently CO,H, -CO 2 alkyl, -C(O)NRR, -N(R 30 )C(O)NRR, -N(R )C(O)-(C -C{)alkoxy, OH, or -NR 6 RT. Embodiment AI9. Compounds according to embodiment AIS, wherein Rs is phenyl, naphthyl, indolyl, pyridyl, quinolinyl, isoquinol inyl, isoindolyl, indol2-onyl, indolyl (CI-C 6 ) alkyl, quinolinyl (CI-C ) alkyl, isoquinolinyl (C!-C ) alkyl, isoindolyl (CI-C ) alkyl, indol-2-onyl (CI-C 6 ) alkyl, pyridazinyl, pyrimidinyl, or pyrazinyl, pyridazinyl(Ci-C ) alkyl, pyrimidinyl(Ci-C 6 ) alkyl, or pyrazinyl (CI-C 6 ) alkyl, each of which is unsubstituted or substituted with i, 2, 3, 4 or 5 groups that are independently CI-C 4 alkyl, halogen, CF 3 , OCF 3 , -CO 2 CH 3 , CI-C 4 hydroxyalkyl, CI-C 4 alkoxy, -CO 2 (CI-Cs alkyl) , benzyloxy, -NRsRg, -C (O) NR RT, NR 6 R CI-C 4 alkyl, and amidinooxime; wherein R and R 7 are independently at each occurrence H, CI-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkoxy CI-C 4 alkyl, CI-C 4 alkanoyl, phenyl CI-C 4 alkyl, phenyl CI-C 4 alkoxy, or phenyl CI-C 4 alkanoyl, wherein each is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, hydroxy, CI- C 4 alkoxy, C:-C 4 alkyl, OH, SH, C 3 -CG cycloalkyl, CF 3 , or OCF 3 ; or Re, Rv, and the nitrogen to which they are attached form a morphol inyl, thiomorphol inyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy CI-C 4 alkyl, or ha!ogen. Embodiment A20. Compounds according to embodiment wherein H, halogen, methyl, ethyl, C 2 -C alkenyl C -C 4 alkvnyl, or carboxaldehyde ; is benzyloxy, OH, phenyloxy, phenyloxy (CI-C 6 ) alkyl, or phenyl (CI-C 4 ) thioalkoxy, wherein each of the above is optionally substituted with i, 2, 3, or 4 groups that are independently halogen, - (C -C ) alkyl-N (R) -C0 2 R 30 , Nervous, NR 6 Rv CI-C 4 alkyl, (CI-C 4 ) haloalkyl, (CI-C 4 ) haloalkoxy, (C 1-C ) alkyl, or pyridyl; and H, (CI-C ) alkyl optionally substituted with one or two groups that are independently C0 2 H, -C0 2 alkyl, -C(O)NRR, -N(R 30)C(O)NRR, -N(R 0 )C(O)- (C 1 -C 6 )alkoxy, OH, or -NR 6 Rv. Embodiment A21. Compounds according to embodiment wherein is phenyl optionally substituted with i, 2, 3, 4, or groups that are independently halogen, CI-C alkyl, - NRI 0 R 11, CI-C 4 alkoxy, -C (O) NRI 0 R 11 , -CO 2 H, NRI 0 R 11 CI-C 4 alkyl, CI-C 6 alkyl, CI-C 6 alkoxycarbonyl, CI-C alkoxy, CHO, -SO 2 NH 2 , C,-C 4 haloalkyl, CI-C hydroxyalkyl, -CI-C 4 alkyl -NR 12 C (0) NRnRI 4 , -CI-C 4 alkyl-NR 12 C (0) - (C 1 -C 4 alkyl) - NRI 3 R 14 -CI-C 4 alkyl-NRi 2 C(O)OR 15 , or -C -C 4 alkyI-NR 12 C(O)- (CI-C 4 alkyl)-Ris, wherein R 10 and Rn at each occurrence are independently H, C -CG alkyl, amino CI-C 4 alkyl, N]4(CI-C alkyl)alkyl, N(CIC alkyl)(CI-C alkyl) CI-C alkyl, CI-C 6 hydroxyalkyl, CI-C alkoxy CI-C alkyl, OH, -SO (C -C alkyl) , or C -C alkanoyl, or R 10, R 11 , and the nitrogen to which they are attached form a piperidiny!, pyrro! idinyl, piperaziny!, or a morpho!inyl ring optionally substituted with ! or 2 groups that are independently alky! or halogen, R 12 is H or CI-C alkyl; Ri 3 and R 14 are independently H or C!-C alky!; or R 13 and R 14 and the nitrogen to which they are attached form a morpholinyl ring; and Ris is CI-C 6 alkoxy; -OC(O)Q-C 6 alkyl, OH. Embodiment A22. Compounds according to embodiment wherein is phenyl optionally substituted with i, 2, 3, 4, or groups that are independently halogen, CI-C 6 alkyl, NRI 0 R 11 , NRI 0 R 11 CI-C 6 alkyl, Ci-C 4 alkoxy, or -C (O) NRIoRn, CO=H, -CI-C 4 alkyl-NR! 0 Rn, CI-C aikyl, CI-C alkoxycarbonyl, C -C 6 alkoxy, CHO, -SO 2 NH 2 , CI-C 4 haloalkyl, CI-C 6 hydroxyalkyl, -CI-C 4 alkyI-NRI 2 C(O)NRI R 14 , -Co-C4 4 alkyl-NR 12 C (O) - (CI-C 4 alkyl) -NRI 3 R 14 , -CI-C 4 alkyl- NR 12 C (O) OR 1 s, or -CI-C 4 alkyl-NR 12 C (0) - (C 1 -C 4 alkyl) -R 1 s wherein R 10 and Rn at each occurrence are independently H, CI-C 6 alkyl, amino CI-C 4 alkyl, NH(C 1 -C alkyl)alkyl, N(C 1 - C alkyl)(Ci-C 6 alkyl) C 1 -C alkyl, CI-C 6 hydroxyalkyl, C 1 -C alkoxy CI-C 6 alkyl, OH, -SO 2 (C 1 -C 6 alkyl) , or CI-C alkanoyl, RI is H or C -C alkyl; R and R are independently H or C -C alkyl; or R and R and the nitrogen to which they are attached form a morpholinyl ring; and Embodiment A23. Compounds according to embodiment A22, wherein Rs is phenyl optionally substituted with i, 2, 3, 4, or groups that are independently halogen, CI-C 6 alkyl, - NR 0 R 1 NRIoR:! C -C 4 alkyl, C - CA alkoxy, -C (0) NR 10 R 11 , wherein R 0 and Rn at each occurrence are independently H, C -C alkyl, amino CI-C 4 alkyl, NH(CI-C 6 alkyl)alkyl, N(CIC 6 alkyl)(CI-C 6 alkyl) CI-C 6 alkyl, C=-C hydroxyalkyl, C -C 6 alkoxy CI-C 6 alkyl, OH, -$0 2 (CI-C 6 aikyl), CI-C 6 alkanoyl. Embodiment A24. Compounds according to embodiment A23, wherein R 5 is phenyl optionally substituted with !, 2, 3, 4, or groups that are independently halogen, C -C 6 alkyl, - NRIoRII, or CI-C 4 alkoxy. Embodiment A25. Compounds according to embodiment A23, wherein R 5 is substituted with at least one -C(O)NRI 0 R 11 . Embodiment A26. Compounds according to embodiment A25, wherein R 10 and R 11 at each occurrence are independently H, CI-C 6 alkyl, amino CI-C 4 alkyl, NH(CI-CG alkyl)alkyl, N(CI-C 6 alkyl) (CIC 6 alkyl) CI-C 6 alkyl, CI-C 6 hydroxyalkyl, CI-C 6 alkoxy CIC 6 alkyl. Embodiment 27. Compounds according to embodiment A26, wherein Embodiment A28. Compounds according to embodiment wherein and R 11 at each occurrence are independently H, C -C a!kyl, -$0 3 (C!-C 6 a!kyl), CI-C alkanoyl. Embodiment A29. Compounds according :o embodiment wherein is phenyl optionally substituted with i, 2, 3, 4, or groups that are independently halogen, CI-C 6 alkyl, k 2 , NH(C 1-C 6 alkyl), N(C 1 -C 6 alkyl) (CI-C a!kyl), CI-C 4 alkoxy, -C(O)N IoRII, wherein each of the above alkyl groups is optionally substituted with 1 or 2 groups that are independently OH, or methoxy; wherein R 0, R and the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, piperazinyl, or a morpholinyl ring optionally substituted with 1 or 2 groups that are independently alkyl or halogen. Embodiment A30. Compounds according to embodiment A20, wherein is phenyl optionally substituted with i, 2, 3, 4, or groups that are independently halogen, CI-C alkyl, CI-C 4 alkoxy, -CO 2 H, -CI-C 4 alkyl-NR 10 R 11 , CI-C 6 alkoxycarbonyl, CI-C alkoxy, CHO, -SO 2 NH 2 , CI -C 4 haloalkyl, CI-C hydroxyalkyl, -CI-C 4 alkyl -NRI 2 C (0) NRI 3 R 14 , -CI-C 4 alkyINR 12 C(O)-(CI-C 4 alkyl)-NRnR 14 , -CI-C 4 alkyI-NRI 2 C(O)OR 15 , or -CI-C 4 alkyI-NRnC(O)-(CI-C 4 alkyl)-Ris, -OC(0)CI-C 6 alkyl, or OH wherein R 12 is H or CI-C 6 alkyl; RI and R 14 are independently H or CI-CG alkyl; or RI and R 14 and the nitrogen to which they are attached form a morpholinyl ring; Compounds according to embodiment Embodiment A31. A30, wherein is phenyl optionally substituted with !, 2, 3, 4, or groups that are independently halogen, C!-C 4 alky!, C -C 4 alkoxy, -C0 2 H, CI-C 4 a!koxycarbony!, C -C 4 alkoxy, CHO, - SO 2 NH 2, CI-C 4 haloalkyl, CI-C 4 hydroxyalkyl. Embodiment A32. Compounds according to embodiment A30, wherein is phenyl optionally substituted with i, 2, 3, 4, or groups that are independently halogen, C -C 4 alkyl, CI-C 4 alkoxy, -CO 2 H, -CI-C 4 alkyl-NR 10 R 11 , -CI-C 4 alkyINRI 2 C(O)NRI 3 RI 4, -CI-C 4 alkyI-NR 12 C(O)-(CI-C 4 alkyI)-NRI 3 R 14 , CI-C 4 alkyl-NR 12 C (O) OR 1 s, or -CI-C 4 alkyl-NR 12 C (O) - (CI-C 4 alkyl)-R 1 s, or-OC(O)CI-C alkyl, wherein R 12 is H or CI-C 6 alkyl; R 13 and R 14 are independently H or C -C 6 alkyl; or R 13 and R 14 and the nitrogen to which they are attached form a morpholinyl ring; R 15 is CI-C 6 alkoxy. Embodiment A33. Compounds according to embodiment A31, wherein is phenyl optionally substituted with i, 2, 3, 4, or groups that are independently halogen, CI-C 4 alkyl, CI-C 4 alkoxy, -CO 2 H, -CI-C 4 alkyl-NR 10 Rn, -CI-C 4 alkyINR 12 C (O) NRI 3 R 14 , -CI-C 4 alkyl-NR 12 C (O) - (CI-C 4 alkyl) -NRI 3 R 14 , where in R 12 is H or CI-C 6 alkyl; RI and R 14 are independently H or C -C 6 a!kyl; or R 13 and R 14 and the nitrogen to which they are attached form a morpholinyl ring. Embodiment A34. Compounds according to any one of embodiments A30, A31, A32, or A33, wherein the pheny! group is substinuted with nwo groups that are meta to each other. Embodiment A35. Compounds according to any one of embodiments A30, A31, A32, or A33, wherein the phenyl group is substituted with two groups that are para to each other. Embodiment A36. Compounds according to embodiment A20, wherein R 5 is indolyl, pyridyl, pyridazinyl, pyrimidinyl, indazolyl, quinolinyl, isoquinolinyl, isoindolyl, indol-2-onyl, pyridazinyl, pyrimidinyl, or pyrazinyl, , each of which is unsubstituted or substituted with i, 2, 3, 4 or groups that are independently CI-C 4 alkyl, halogen, CF 3 , • OCF 3 , -CO 2 CH CI-C 4 hydroxyalkyl, CI-C 4 alkoxy, -COs(CI-C alkyl), benzyloxy, NRsRg, NReR 7 C 1 -C 4 alkyl, -C(O)NR 6 RT, or amidinooxime; wherein Re and R are independently at each occurrence H, CI-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkoxy Ci-C 4 alkyl, CI-C 4 alkanoyl, phenyl Ci-C 4 alkyl, phenyl CI-C 4 alkoxy, or phenyl CI-C 4 alkanoyl, wherein each is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, OH, SH, C 3 -C cycloalkyl, CI-C 4 alkoxy, C -C 4 alkyl, OH, CF 3 , or OCF 3; or Re, R and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment A38. Compounds according to embodiment wherein indolyl, pyridyl, pyrimidinyl, indazolyl, or pyrazinyl, each of which is unsubstituted or substituted with i, 2, 3, or 4 groups that are independently C:-C 4 alky!, halogen, CF 3 , OCF 3 , - CO=CH 3 , CI-C hydroxyal kyl, CI-C alkoxy, -C0 2 (CI-Cs alkyl) , benzyloxy, -C (O) NR R -NRsRg, NR 6 R 7 CI-C 4 alkyl, and amidinooxime; wherein R 6 and Rv are independently at each occurrence H, CI-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkoxy CI-C 4 alkyl, CI-C 4 alkanoyl, phenyl CI-C 4 alkyl, phenyl CI-C 4 alkoxy, or phenyl CI-C 4 alkanoyl, wherein each is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF or OCF 3. Embodiment A39. Compounds according to embodiment wherein is indolyl, pyridyl, or pyrazinyl, each of which is unsubstituted or substituted with I, 2, 3, or 4 groups that are independently CI-C 4 alkyl, halogen, CF OCF - CO 2 CH 3 , CI-C 4 hydroxyal kyl, CI -C 4 alkoxy, -COs (CI-Cs alkyl) , benzyloxy, -C (O) Nervous, N]{,R 9 , NR RT-CI-C 4 alkyl -, and amidinooxime ; wherein R and R 7 are independently at each occurrence H, CI-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkoxy CI-C 4 alkyl, each of which is optionally substituted with I :i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 alkoxy, C -C 4 Embodiment A40. Compounds according to embodiment A36, wherein R is indolyl, pyridy!, pyridazinyl, pyrimidinyl, or pyrazinyl, each of which is unsubstituted or substituted with !, 2, 3, 4 or 5 groups ha are independently C -C a!ky!, halogen, CF OCF 3 , - C0 2 CH 3 , CI-C 4 hydroxyaikyl, C -C 4 alkoxy, -C0 2 (CI-C alkyl), benzyloxy, -C(O) H 2 , -C (O) NH (C=- C 6 a!kyl) wherein the alkyl group is optionally substituted with OH or methoxy, -C(O)N(CI-C 6 alkyl) (CI-C 6 alkyl) wherein each alkyl group is independently and op ional!y substituted with OH or methoxy, -C(O)NR R NReRg, NR R 7 Ci-C 4 alkyl, -CI-C 4 alkyl-NH=, -CI-C 4 alkyINH(C:-C alkyl) wherein each alkyl group is independently and optionally substituted with OH or methoxy, -CI-C 4 alkyl-N(C 1-C alkyl) (C -C 6 alkyl) wherein each alkyl group is independently and optionally substituted with OH or methoxy, and amidinooxime; wherein R 6, R and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, or piperazinyl ring which is optionally substituted with i or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy Ci-C 4 alkyl, or halogen. Embodiment A42. Compounds according to any one of embodiments A37, A38, A39, or A40, , wherein RI is H, halogen, methyl, or carboxaldehyde; R 2 is benzyloxy, phenyloxy, phenyloxy(Ci-C 6 )alkyl, or phenyl (CI-C 4) thioalkoxy, wherein each of the above is optionally substituted with I, 2, 3, or 4 groups that are independently halogen, - (Ci-C 6 ) alkyl-N (R) -C0 2 R 30 , NR RT, (CI-C 4) haloalkyl, (CI-C 4 ) haloalkoxy, (CI-C ) alkyl, NRGRv (CI - CG ) al kyl, pyridyl, morphol inyl, thiomorphol inyl, piperaziny! pyridyl (CI-C 6 ) alkyl, morpholinyl (CI-C 6 ) alkyl, thiomorpholinyl (Q-CG) alkyl, or piperazinyl (C:-C 6 )alkyl wherein the pyridyl, morpholiny!, thiomol-pho!iny!, and piperazinyl rings are optionally substituted with 1 or 2 groups that are independently C:-C 4 alkyl, or halogen; wherein R 6 and R 7 are independently at each occurrence H, C:-C alkyl optionally substituted with 1 or two groups that are independently OH, halogen or methoxy, CI-C 4 hydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkoxy C -C 4 alkyl, CI-C 4 alkanoyl, benzyl, benzyloxy, or phenyl CI-C 4 alkanoyl, wherein each is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, OH, SH, C 3 -C 6 cycloalkyl, C - C 4 alkoxy, CI-C 4 a!kyl, CF 3 , or OCF 3 , and H, (CI-C 3 ) alkyl optionally substituted with one or two groups that are independently CO,H, -CO 2 alkyl, -C(O)NRR, -N(R 0)C(O)NRR, -N(R 30 )C(O)- (Ci-C )alkoxy, -NR 6 R NR 6 RvCI-C 4 alkyl, or hydroxy(Ci-C 3 )alkyl. Embodiment A43. Compounds according to embodiment wherein H or halogen. Embodiment A44. Compounds according to embodiment wherein phenyl(Ci-CG)alkyl, (Ci-C )alkyl, piperidinyl(Ci-C ), alkyl, thienyl(Ci-C ) alkyl, indolyl (CI-C 6 ) alkyl, naphthyl (CIC 6) alkyl, pyridyl (CI-C ) alkyl, pyrimidyl (CI-C ) alkyl, quinolinyl (CI-C ) alkyl, isoquinolinyl (CI-C ) alkyl, isoindolyl (CI-C 6 ) alkyl, indo1-2 -onyl (CI-C 6 ) alkyl, pyridazinyl (CI-C 6 ) alkyl, pyrazinyl (CI-C ) alkyl, or pyrazinyl(Ci-C )alkyl, wherein each of the above is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently alkyl, hal ogen, a ! koxy, ben zyl oxy, hydr exya i ky!, thioalkoxy, -C0 2 (C -C 5 alkyl) , CO 2 H, CN, amidinooxime, NRsRg, NR RT-(C!-C 6 alkyl) -, -C (O) kTR R amldino, CF or OCF ; R 8 is hydrogen, CI-C 6 a!kyl, C -C 6 alkanoy!, phenvl CI-C 6 alkyl and pheny! C!-C 6 alkanoyi; and R 9 is aminoalkyl, mono C 1 -C alkylamino C:-C 6 alkyl, di Ci- C 6 alkylamino e 1 -c 6 alkyl, C 1 -C alkyl, Ci-C alkanoyl, pheny! C 1 -C 4 alkyl, indazolyl, and phenyl C 1 -C 4 alkanoyl. In this embodiment, it is preferred that when R 2 is benzyloxy, R 4 is H, and R is benzyl or methyl, RI is not hydrogen; and no more than two of RI, R 2 , R 4 , and R 5 are simultaneously hydrogen. Embodiment A45. Compounds according to embodiment A44, wherein Rs is phenyl(Ci-C 6 )alkyl, which is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently alkyl, halogen, alkoxy, benzyloxy, thioalkoxy, -CO 2 (CI-Cs alkyl), CO 2 H, CN, amidinooxime, NRsRg, NR RT-(CI-C alkyl)-, -C(O)NR 6 Rv, amidino, CF 3 , or OCF 3 ; wherein R 6 and R 7 are independently at each occurrence H, CI-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkoxy CI -C 4 alkyl, CI-C 4 alkanoyl, phenyl CI-C 4 alkyl, phenyl CI-C 4 alkoxy, or phenyl CI-C 4 alkanoyl, wherein each is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, CF 3 , or OCF 3 ; R 6, Rv, and the nitrogen to which they are attached form a morpholiny!, thiomoroholiny!, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen; R 8 is hydrogen, C -C 6 alkyl, CI-C 6 alkanoyl, phenyl CI-C 6 alkyl and phenyl C -C 6 alkanoy!; and R 9 is aminoalkyl, mono CI-CG alkylamino CI-C 6 alkyl, di CIC 6 alkylamino CI-C 6 a!kyl, CI-C 6 a!kyl, CI-C 6 alkanoyl, phenyl C -C 4 alkyl, indazolyl, and phenyl CI-C 4 a!kanoyl. Embodiment A4 6. Compounds according to embodiment wherein pheny!(Ci-C )alkyl, which is unsubstituted or substituted with !, 2, 3, 4, or 5 groups that are independently CN, halogen, C -C 4 alkoxy, CI-C 4 thioalkoxy, C!-C 4 haloalkyl, CI-C 4 alkyl, CI-C 4 haloalkyl, CI-C 4 haloalkoxy, -C (O) NR 20 R 21 , wherein R 20 and Rn are independently H, CI-C alkyl, CI-C hydroxyalkyl, CI-C 6 alkoxy CI-C 6 alkyl, or R 20, R 21 , and the nitrogen to which they are attached form a piperazinyl, or morpholinyl ring, each of which is optionally substituted with 1 or 2 groups that are independently alkyl or halogen. Embodiment A47. Compounds according to embodiment wherein phenyl(Ci-C 4 )alkyl, which is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently CN, halogen, CI-C 4 alkoxy, CI-C 4 haloalkyl, CI-C 4 alkyl, CI-C 4 haloalkoxy, -C(O)NR 20 Rn, wherein R 20 and R 2 ! are independently H, Ci-C 6 alky!, Ci-C 6 hydroxya!ky!, C!-C 6 a!koxy CI-C alkyl, or R 20, R 21 , and the nitrogen to which they are attached form a piperazinyi, or morpholinv! ring, each of which is optionally substituted with 1 or 2 groups that are independently alkyl or halogen. Embodiment A48. Compounds according to embodiment wherein is benzyl or phenethyl, each of which is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently CN, halogen, Cz-C 4 a!koxy, CF 3 , OCF Cz-C 4 a!ky!, -C (O) NR 20 R 21 , wherein R 20 and R 21 are independently H, C -C 6 alkyl, CI-CG hydroxyalky!, CI-C 6 alkoxy C:-C alkyl, or R 20, R 21 , and the nitrogen to which they are attached form a piperazinyl, or morpholinyl ring, each of which is optionally substituted with 1 or 2 groups that are independently alkyl or halogen. Embodiment A49. Compounds according to embodiment wherein benzyl or phenethyl, each of which is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently halogen, methoxy, ethoxy, CF OCF 3 , methyl, ethyl, or-C(O)NR 20 R 21 , wherein R 20 and Rn are independently H, CI-CG alkyl, CI-C 6 hydroxyalkyl, CI-C 6 alkoxy CI-C 6 alkyl, Embodiment A50. Compounds according to embodiment wherein benzyl or phenethyl, each of which is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently halogen, methoxy, ethoxy, CF OCF 3 , methyl, ethyl, or -C(O)NR 20 R 21 , wherein R 20, R 21 , and the nitrogen to which they are attached form a piperazinyl, or morpho!inyl ring, each cf which is optionally substituted with 1 or 2 groups ha are independently alkyl or halogen. Embodiment A51. Compounds according to embodiment wherein is substituted on the phenyl ring with !, 2, 3, 4, or groups and wherein there is a group at the para position of the phenyl. Embodiment A52. Compounds according to embodiment wherein is piperidinyl(Ci-CG) alkyl, thienyl(Ci-C 6 ) alkyi, indolyl (CI-C ) alkyl, pyridyl (C -C ) a!ky!, pyrimidyl (CI-C 6 ) alkyl, quinolinyl (CI~C 6 ) alkyl, isoquinolinyl (CI-C 6 ) alkyl, isoindolyl (CI~C 6 ) alkyl, indol-2-onyl (CI-C 6 ) alkyl, pyridazinyl (CI-CG) alkyl, or pyrazinyl (CI-C 6 ) alkyl, or pyrazinyl(C 1-C )alkyl, or pyrazinyl(C 1 -C 6 )alkyl, wherein each of the above is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently CI-C 6 alkyl, halogen, CI-C 6 alkoxy, CI-C 6 hydroxyalkyl, benzyloxy, CI-C thioalkoxy, -CO 2 (CI-Cs alkyl) , CO 2 H, CN, amidinooxime, NRsRg, NR 6 R - (CI-C alkyl) -, -C (O) NR 6 Rv, amidino, CF 3 , or OCF ; R 8 is hydrogen, C -C alkyl, CI-C 6 alkanoyl, phenyl CI-C alkyl and phenyl CI-C 6 alkanoyl; and R 9 is aminoalkyl, mono CI-C 6 alkylamino CI-C 6 alkyl, di CIC alkylamino CI-C alkyl, CI-C alkyl, CI-C 6 alkanoyl, phenyl CI-C 4 alkyl, indazolyl, and phenyl CI -C 4 alkanoyl. In this embodiment, it is preferred that when R 2 is benzy!oxy, R is H, and R is bennyl or methyl, RI is not hydrogen; and no more than two of RI, R 2 , R 4 , and Rs are simu!taneous!v hydrogen. Embodiment A53. Compounds according to embodiment A52, wherein R 5 is piperidinyl (Ci-C 4 ) a!kyl, thienyl (C;-C 4 ) alkyl, indolyl (C 1-C ) alkyl, pyridy! (CI-C 4 ) alkyl, pyrimidyl (C 1 -C 4 ) alkyl, or pyrazinyl(C 1 -C 4 )alkyl, each of which is unsubstituted. Embodiment A54. Compounds according to embodiment A52, wherein R S is indolyl (Ci-C 4 ) alkyl, pyrimidyl(C 1 -C 4 )alkyl, or pyrazinyl(C 1-C 4)aikyl, wherein each of the above is unsubstituted or substituted with i, 2, 3, or 4 groups that are independently CI-Ce alkyl, halogen, e 1 -c 6 alkoxy, C 1 -Ce hydroxyalkyl, benzyloxy, C 1-Ce thioalkoxy, -CO 2 (C 1 -Cs alkyl ) , C0 2 H, CN, amidinooxime, NRsR 9 , NR 6 RT- (Ci-C 6 alkyl) -, amidino, -C (O) NR 20 R 21 , CF 3 , or OCF ; wherein Re and R 7 are independently at each occurrence H, CI-C 4 alkyl, CI-C 4 hydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkoxy CI-C 4 alkyl, CI-C 4 alkanoyl, benzyl, benzyloxy, or phenyl CI-C 4 alkanoyl, wherein each is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, OH, SH, C 3 -Ce cycloalkyl, CIC 4 alkoxy, CI-C 4 alkyl, CF 3 , or OCF 3 ; or Re, RT, and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently Ci-C 4 alkyl, hydroxy, hydroxy Ci-C 4 alkyl, or halogen; Re is hydrogen, Ci-C 6 alkyl, CI-C alkanoyl, phenyl Ci-C 4 a!kyl and phenyl C- -C alkanoyl; and R 9 is aminoa!kyl, mono CI-C 6 alkylamino CI-C alkyl, di Ci-C 6 alkylamino CI-C 6 a!kyl, CI-C alkyl, CiC 6 alkanoyl, phenyl Ci-C 4 alky!, indazolyl, and phenyl Ci-C 4 alkanoyl; R 20 and Rn are independently H, Ci-C 6 a!kyl, Ci-C 6 hydroxyalky!, Ci-C 6 alkoxy Ci-C 6 alkyl, or R 20, R 2 i, and the nitrogen to which they are attached form a piperazinyl, or morpholinyl ring, each of which is optionally substituted with 1 or 2 groups that are independently alkyl or halogen Embodiment A55. Compounds according to embodiment wherein indolyl (Q-C 4 ) alkyl, or pyrazinyl(Q-C 4 )alkyl, wherein each of the above is unsubstituted or substituted with i, 2, 3, or 4 groups that are independently Ci-C alkyl, halogen, Ci-C 6 alkoxy, CI-C 6 hydroxyalkyl, benzyloxy, Ci-C 6 thioalkoxy, -CO 2 (CI-C 5 alkyl), CO 2 H, CN, -C(O)NR 20 R 2 i, CF or OCF 3 ; wherein R= 0 and Rn are independently H, Ci-C alkyl, CI-C hydroxyalkyl, Ci-C alkoxy CI-C alkyl, or R 20, R 2 i, and the nitrogen to which they are attached form a piperazinyl, or morpholinyl ring, each of which is optionally substituted with 1 or 2 groups that are independently alkyl or halogen. Embodiment A56. Compounds according to embodiment wherein Rs is isoquinolinyl, isoindolyl, idol-2-onyl, quinolinyl (CIC 6) a!kyl, isoquinolinyl (C:-C 6 ) alkyl, isoindoly! (C:-C alkyl, indo!-2-onyl(C -C ) alkyl, wherein each of the above is unsubstituted or substituted with ! 2, 3, 4, or 5 groups that are independently CI-C 6 aikyl, halogen, C -C 6 alkoxy, Ci-C 6 hydroxyalkv I, benzyloxy, CI-C 6 thioa!koxy, -CO 2 (C -Cs alkyl) , C0 2 H, CN, amidinooxime, NRBRg, NR 6 RT- (C 1 -C 6 alkyl) -, -C (O) NR 6 R amidino, CF 3 , or OCF Embodiment A57. Compounds according to embodiment AI, wherein R 1 is H, halogen, methyl, ethyl, C 2 -C 4 alkenyl C 2 -C 4 alkynyl, or carboxaldehyde; R 2 is benzyloxy, OH, phenyloxy, phenyloxy CI-C 6 ) alkyl, or phenyl (CI-C 4 ) thioalkoxy, wherein each of the above is optionally substituted with I, 2, 3, or 4 groups that are independently halogen, - (CI-C 6 ) alkyl-N (R) -C0 2 R 0 , NR 6 R (C -C 4) haloalkyl, (CI-C 4 ) haloalkoxy, (CI-C 6 ) alkyl, pyridyl, or NR Rv- (CI-C alkyl)-; and R 4 is H, (CI-C 4 ) alkyl optionally substituted with one or two groups that are independently C0 2 H, -C0 2 alkyl, -C(O)NRR, - N (R 30 ) C (0) NRR, -N(R 30 ) C (0) - (CI-C 6 ) alkoxy, or -NR 6 R or hydroxy (CI-C 4 ) alkyl ; Rs is C -Cv cycloalkyl or C 3 -Cv cycloalkylalkyl, each of which is optionally substituted with 1 or 2 groups that are independently alkyl, alkoxy, halogen, -NR 6 Rv, or NRGRT- (CIC alkyl)-, wherein each of the alkyl groups is optionally substituted with 1 or 2 groups that are independently OH, methoxy, NH 2 , or halogen. Embodiment A58. Compounds according to embodiment A57, wherein C -C cycloalkyl or C 3 -C 7 cycloalkyl C -C 4 a!kyl, each of which is optionally substituted with i or 2 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, halogen, - h-R RT, or NR 6 R -(CI-C 6 alkylwherein each of the alkyl groups is optionally substituted with 1 or 2 groups that are independently OH, methoxy, or N-H=; and R are independently at each occurrence H, CI-C 4 alkyl, C -C 4 hydroxyalkyl, CI-C 4 alkoxy, CI-C 4 alkoxy CI-C 4 alkyl, C -C 4 al kanoyl, benzyl, benzyloxy, or phenyl C 1 -C 4 alkanoyl, wherein each is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, OH, SH, C 3 -C cycloalkyl, CI-C 4 alkoxy, C -C 4 alkyl, CF 3 , or OCF 3; or R and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment A59. Compounds according to embodiment wherein H, halogen, methyl, ethyl; is benzyloxy, phenyloxy, phenyloxy (C 1 -C ) alkyl, or phenyl (CI-C 4) thioalkoxy, wherein each of the above is optionally substituted with i, 2, 3, or 4 groups that are independently halogen, - (CI-C 6 ) alkyl -N (R) -CO 2 R 30 , amino, mono or dialkylamino, -NR 6 RT, (CI-C 4 ) haloalkyl, (CI-C 4 ) haloalkoxy, (Ci-C 6 ) alkyl, or Nroff-(CI-C alkyl)-; and is H, methyl, (Q-C 4 )alkyl optionally substituted with one or two groups that are independently CO 2 H, -C0 2 alkyl, -C(O)NRR, -N(R 0 )C(O)NRR, -N(R] 0 )C(O)- (Ci-C 6 )alkoxy, or - NR R or hydroxy(Ci-C 2 )alkyl. Embodiment A60. Compounds according to embodiment A59, wherein R 2 is substituted with two halogens and is further optionally substituted with 1 or 2 groups nhat are independently halogen, - (CI-C ) aikyi-N (R) -CO,R 30 , amino, mono or dialkylamino, -NR R (CI-C 4 ) ha!oalkyl, (C -C ) haloalkoxy, (CI-C 6 ) alkyl, or NR Rv- (CI-C alkyl) . Embodiment A61. Compounds according to embodiment AI, wherein R 5 is H, alkyl optionally substituted with i, 2, or 3 groups that are independently phenylalkoxycarbonyl, -NRsRg, halogen, -C(O)NRBRg, alkoxycarbonyl, or alkanoyl, alkoxyalkyl optionally substituted with one trimethylsilyl group, alkoxycarbonyl, amino, hydroxyalkyl, alkenyl optionally substituted with alkoxycarbonyl, alkynyl, -SO 2 -alkyl, or alkoxy optionally substituted with one trimethylsilyl group, whereln each of the above is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently alkyl, halogen, alkoxy, phenylalkoxy, thioalkoxy, -SO 2 alkyl, alkoxycarbonyl, phenylalkoxycarbonyl, C0 2 H, CN, OH, amidinooxime, NR,Rg, NR 6 R -(CI-C 6 alkyl)-, -C(O)NR R amidino, hydroxyalkyl, carboxaldehyde, -NR 6 RT, haloalkyl, or haloalkoxy; wherein R 8 is hydrogen, alkyl, alkanoyl, phenylalkyl and arylalkanoyl; and wherein R 9 is alkyl, alkanoyl, phenylalkyl, heteroaryl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, and arylalkanoyl. In this embodiment, it is preferred that when R 2 is benzyloxy, R 4 is H, and R 5 is benzyl or methyl, RI is not hydrogen; and no more than two of R Rz, R 4 , and Rs are simultaneously hydrogen. Compounds according to embodiment A!, Embodiment A62. wherein Rs is H, alkyl optionally substituted with !, 2, or 3 groups that are independently phenyla!koxycarbony!, -NRsRg, ha!ogen, -C(O)NRsRg, alkoxycarbonyl, or alkanoyl, substituted with one alkoxya!ky! optionally alkoxycarbonyl, amino, trimethylsilyl group, hydroxyalkyl, alkenyl optionally substituted with alkoxycarbonyl, alkynyl,-S0 2-alkyl, alkoxy optionally substituted with one trimethylsilyl group, wherein each of the above is unsubstituted or substituted with 1 2, 3, 4, or 5 groups that are independently alkyl halogen, alkox-y, phenylalkoxy, thioalkoxy, -SO 2 alkyl alkoxycarbonyl, phenylalkoxycarbonyl, CO,H, CN, OH amidinooxime, NRsRg, NR R -(CI-C alkyl)-, -C(O)NR 6 R 7 amidino, hydroxyalkyl, carboxaldehyde, -NR R 7 haloalkyl, or haloalkoxy; wherein R 6 is hydrogen, alkyl, alkanoyl, phenylalkyl and arylalkanoyl; and wherein R 9 is alkyl, alkanoyl, phenylalkyl, heteroaryl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, and arylalkanoyl. In this embodiment, it is preferred that when R 2 is benzyloxy R 4 is H, and Rs is benzyl or methyl, R! is not hydrogen; and no more than two of RI, R 2 , R 4 , and Rs are simultaneously hydrogen. Embodiment A63. Compounds according to embodiment A62, wherein H, halogen, methyl, ethyl, C 2 -C 4 alkenyl, C:-C€ a!kynvl, or carboxaldehyde, is benzyloxy, OH, phenyloxy, pheny!oxy (C 1 -C 6 ) aikyl, or phenyl (C -C 4 ) thioa!koxy, wherein each of the above is optionally substituted with I, 2, 3, or 4 groups that are independently halogen, - (C:-C 6 )a!ky!-N(R) -C0 2 R 30 , NR 6 R (CIC 4 ) haloalkyl, (CIC 4 ) haloalkoxy, (CI-C ) alkvl, pyridyl, or NR 6 R:- (CI-C 6 alkyl) -; and H, (CI-C 4 ) alkyl optionally substituted with one or two groups that are independently C0 2 H, -C0 2 alkyl, -C(O)NRR, N(R 0)C(O)NRR, -N(R 0 )C(O)- (C 1 -CG)alkoxy, or -NR 6 R or hydroxy ( C 1 - C 4 ) a I kyl. Embodiment A64. Compounds according to embodiment wherein H, a!ky! optionally substituted with I, 2, or 3 groups that are independently phenylalkoxycarbonyl, -lqRsRg, halogen,-C(O)NRaRg, alkoxycarbonyl, or alkanoyl, alkoxyalkyl optionally substituted with one trimethylsilyl group, alkoxycarbonyl, amino, hydroxyalkyl, alkenyl optionally substituted with alkoxycarbonyl, alkynyl,-S0 2-alkyl, alkoxy optionally substituted with one trimethylsilyl group, wherein wherein R 8 is hydrogen, CI-C 4 alkyl, CI-C 4 alkanoyl, phenyl CI-C 4 alkyl and phenyl CI-C 4 alkanoyl; wherein R 9 is CI-C 4 alkyl, C -C 4 alkanoyl, phenyl CI-C 4 alkyl, pyridyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, and phenyl CI-C 4 alkanoyl. Embodiment A65. Compounds according to embodiment wherein CI-C alkyl optionally substituted with i, 2, or 3 groups that are independently phenyl CI-C 4 alkoxycarbonyl, N-H 2 , mono CI-C 4 alkylamino, di C -C 4 alkylamino, halogen, -C (0) NH 2 , -C (0) k (C!- C 6 alkyl) wherein the alkyl is optionally substituted with OH, ATH.z, or methoxy, -C(O)N (C:-CG alkyl) (CI-C 6 alkyl) wherein each alkyl is op-_ionally substituted with OH, N-H 2 , er methoxy, C:-C alkoxycarbonyl, and CI-C 4 alkanoyl, or CI-C 4 alkoxy CI-C alkyl, CI-C 4 alkoxycarbonyl, amino, C - C hydroxya!kyl, C 2 -C 4 alkenyl optionally substituted with CI-C 4 a!koxycarbonyl, C 2 -C 4 alkynyl, -S0 2 - CI-C 4 alkyl, or C -C 4 alkoxy. Embodiment A66. A compound of the formula H R 1 R 4" I Rs pharmaceutically acceptable salt thereof, wherein is halogen, NO 2 , a!kyl, carboxaldehyde, hydroxyalkyl, arylalkoxy, aryla!kyl, CN, aryl, alkanoyl, alkoxy, alkoxyalkyl 0 haloalkyl, or arylalkanoyl, wherein the aryl portion of arylalkoxy, arylalkyl, and arylalkanoyl is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently halogen, (C -C 4)alkyl, (CI-C 4 ) alkoxy, nitro, CN, haloalkyl, haloalkoxy or C0 2 H; wherein the alkyl portion of the alkyl, hydroxyalkyl, arylalkoxy, arylalkyl, alkanoyl, alkoxy, alkoxyalkyl and arylalkanoyl groups is unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, CI-C 4 alkoxy, CI-C 4 alkoxycarbonyl, or spirocyclopropyl; aryl, heteroaryl, ary!alkenyl, arylalkoxy, aryloxyalkyl, arylalkyl, OH, alkynyl, aryloxy, aryloxyalkyl, arylthioalkoxy, alkoxy, -OC (O) NH (CH=) naryl -OC (0)N (alkyl) (CH 2 ) acrylic, -0SO 2 (CI-CE) a!ky!, -OSQary! alkyl, alkoxya!koxy, k 6 Rg, or CO,H, wherein n is 0, I, 2, 3, 4, 5 or 6; each of the above is unsubstituted or substituted with ! 2, 3, 4, or 5 groups that are independently halogen -(Q-C 6-SQ-C6)alky!-N 2 R 30, alkoxy, alkoxycarbonyl, CN NR R haloa!kyl, haloa!koxy, aikyl, heteroaryl heteroary!alky!, NR RT-(C!-C 6 alkyl)-, phenyl, -SO 2 - phenyl wherein the phenyl groups are optionally substituted with i, 2, or 3 groups that are independently halogen or NO 2 ; or -OC(O)NR 6 R wherein R 6 and R are independently at each occurrence H, alkyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, SO 2-alkyl, OH, hydroxyalkyl, -(C 1 -C 4 )alkyl-CO 2 - alkyl, heteroarylalkyl, alkanoyl, arylalkyl, arylaikoxy, or arylalkanoyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, alkoxy, heterocycloalkyl, OH, SH, C 3 -C cycloalkyl, NH 2 , NH(alkyl), N(alkyl) (alkyl), -Oalkanoyl, alkyl, haloalkyl, or haloalkoxy; or R Rv, and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen; R at each occurrence is independently H or CI-C alkyl; R 0 is CI-C 6 alkyl optionally substituted with 1 or 2 groups that are independently OH, SH, halogen, amino, monoalkylamino, dialkylamino or C -C cycloalky!; is H, alkyl optionally substituted with one or two groups that are independently C0 2 H, -C0 2 alkyl, -C(O)NRR, N(R 30)C(O)NRR, -N(R 30 )C(O]-(Ci-C )alkoxy, or -NR 6 R arylalkoxy, arylalkyl, hydroxya!kyl, haloalkyl, alkoxy, carboxaldehyde, C0 2 H, a!koxyalkyl, or alkoxya!koxy, wherein the aryl portion of arylalkoxy, aryla!kyl is unsubstituted or substituted with i, 2, 3, 4, or groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, haloalkyl, or haloalkoxy; and H, arylalkyl, alkyl, aryl, alkoxy, heterocycloalkylalkyl, heteroary!alkyl, heterocycloalkyl, cycloalkyl, cycloalkylalkyl, -alkyl-S-aryl, -alkyl-SO -aryl, -(CI-C 4 ) alkyl-C(O)-heterocycloalkyl, -S0 2 -aryl, or heteroaryl, wherein each of the above is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently alkyl, halogen, alkoxy, aryl, arylalkoxy, thioalkoxy, alkoxycarbonyl, arylalkoxycarbonyl, OH, C0 2 H, CN, amidinooxime, NRsRg, N-RGR - (CI-C alkyl) -, -C (O)NR 6 R - (Ci-C 4 alkyl) -C (0) NR 6 RT, amidino, hydroxyalkyl, - SO 2 alkyl, -SO 2 H, - SO 2 NRGR 7, -NR Rv, alkanoyl wherein the alkyl portion is optionally substituted with OH, halogen or alkoxy, haloalkyl, -(CI-C 4 alkyI)- NRIsC(O)NRI 6 RI -(CI-C alkyI)-NRIsC(O)R 18 , -O-CH 2 -O, O-CH 2 CH 2-O-, or haloalkoxy; wherein Re at each occurrence is independently hydrogen, alkyl, alkanoyl, arylalkyl and arylalkanoyl wherein each of the above is optionally substituted with I, 2, 3, 4, or 5 groups that are independently a!kyl, a!ko×y, alkoxycarbonyl, halogen, or ha!oalkyl; and R 9 at each occurrence is independently alkyl 0 alkanoyl, arylalkyl cyc!oalkyl, a!keny! 0 heteroaryl, cycloalkyla!kyl, aryla!kanoyl, -SO=- phenyl, and ary1 wherein each of the above is optionally substituted with i, 2, 3, 4, or groups that are independently alkyl, aikoxy, alkoxycarbonyl, halogen, or haloalkyl; R!s is H or C -C 6 alkyl; R 16 and RI are independently H or CI-C alkyl; or RI R 17 , and the nitrogen to which they are attached form a morpholinyl ring; and RiB is CI-C 6 alkyl optionally substituted with -O-(C 2 - C 6 alkanoyl, C 1 -C 6 hydroxyalkyl, CI-C 6 alkoxy, Ci-C 6 alkoxy C 1 -C 6 alkyl; amino C 1 -C alkyl, mono or dialkylamino CI-C 6 alkyl. In this embodiment, it is preferred that: R 6 and R are not simultaneously OH; R 6 and R 7 are not simultaneously -SO 2 (C -C alkyl) ; when R 2 is OH, R 4 is methyl and R 5 is phenyl, RI is not acetyl; and R 4 and Rs are not simultaneously hydrogen. Embodiment A71. Compounds according to embodiment A66 wherein R 1 is halogen, CI-C alkyl, phenyl, carboxaldehyde, C 1 -C hydroxyalkyl, phenyl Ci-C 6 alkoxy, phenyl C 1 -C alkyl, CN, CI-C 6 alkanoyl, C -C 6 alkoxy, CI-C 6 alkoxy C -C alkyl, CI-C 6 haloalkyl, or phenyl CI-C 6 alkanoyl, wherein the above phenyl groups are unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, (C:-C )alkyl, (C 1 -C ) alkoxy, nitro, CN, CI-C 4 haloalkyl, C -C haloalkoxy or C0 2 H; wherein the above alkyl groups are unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, methoxy, or ethoxy, is phenylalkoxy, OH, phenyloxy, pheny!oxy (CI-C ) alkyl, phenylthio (CI-C 4 ) alkoxy, alkoxy, alkenyl, phenethyl, -OC (0) NH (CH 2 ) nphenyl, -OC (0) N (alkyl) (CH 2 ) nphenyl, alkyl, alkoxyalkoxy, NRsR 9 , pyridyl, pyrimldyl, pyridazyl, pyrazolyl, imidazoly!, pyrroly!, tetrahydroquinolinyl, amino, tetrahydroisoquinolinyl, tetrazoly!, pyrazinyl, benzimidazolyl, triazinyl, tetrahydrofuryl, piperidinyl, hexahydropyrimidinyl, thiazolyl, thienyl, or C0 2 H, wherein n is 0, I, 2, or 3; each of the above is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently halogen, -(CI-C )alkyI-N(R)-CO R 30, haloalkyl, haloalkoxy, alkyl, thienyl, pyridy!, or phenyl optionally substituted with i, 2, or 3 halogens; R 6 and R are independently at each occurrence H, alkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, alkoxycarbonyl, - (Ci-C 4)alkyl-CO 2-alkyl, alkanoyl, phenylalkyl, phenylalkoxy, or phenylalkanoyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, OH, SH, C 3 - C cycloalkyl, alkoxy, NH 2 , NH(CI-C 6 alkyl),. N(CI-C alkyl) (CI-C 6 alkyl), alkyl, CF 3 or OCF 3 ; or R 6, RT, and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with i or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen; is H, alky! optionally substituted with one or two groups tha are independently C0 2 H, -COzaiky!, -C(O)NRR, N(R 30)C(O)NRR, -N(R 0 )C(O)-(C 1 -C 6 )alkoxy, or -NR R:, phenylalkoxy, phenylalky!, hydroxyalkyl, carbexaldehyde, ha!oalkyl, alkoxy, alkoxyalkyi, or alkoxya!koxy, wherein the above pheny! groups are unsubstituted or substituted with i, 2, or 3 groups tha are independently halogen, hydroxy, alkoxy alkyl, nitro, haloalkyl or haloalkoxy; and is benzyl, phene hyl,(CI-C alky!, phenyl, naphthy! alkoxy, piperidiny!, pyrrolidinyl, imidazolidinyl piperazinyl, isoquinolinyl, tetrahydroisoquinolinyl, indolyl,!Hinda zolyl, pyridyl, pyrimidyl, pyridazyl, pyrazinyl, piperidinyl (Ci-C 6 ) alkyl, pyrrolidinyl (C 1 - C 6)alkyl, imidazolidinyl (Ci-C 6 ) alkyl, piperazinyl (C 1 - C )alkyl, pyridyl (CI-C 6 ) alkyl, pyrimidyl (Ci-C 6 ) alkyl, pyridazyl (Ci-C 6 ) alkyl, pyrazinyl (Ci-C 6 ) alkyl, isoquinolinyl (CI-C 6 ) alkyl, tetrahydroisoquinoliny] (C 1 - C )alkyl, indolyl(C 1 -CG)alkyl, or iH-indazolyl(C 1 -C )alkyl, and wherein each of the above is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently alkyl, halogen, alkoxy, hydroxyalkyl, phenylalkoxy, thioalkoxy, alkoxycarbonyl, phenylalkoxycarbonyl, OH, CO 2 H, CN, amidinooxime, NRsRg, NR 6 Rv-(C 1 -C alkyl)- , -C(O)NRGR amidino, piperazinyl, morpholinyl, -SO 2 (CI-C 6) alkyl, -SO 2 NH 2 , -SO 2 NH(C 1 -C 6 )alkyl, -SO 2 N(C 1 - CG)alkyl (C 1 -CG)alkyl, haloalkyl, or haloalkoxy. In this embodiment, it is preferred that when R 2 is OH, R 4 methyl and Rs is phenyl, RI is not acetyl; and and Rs are not simultaneously hydrogen. Embodiment A72. Compounds according to embodiment A7! wherein RI is halogen, alkyl, carboxa!dehyde, hydroxyalkyl, phenylalkoxy, phenyl, benzy!, phenethyl, phenpropyl, phenbutyl, CN, (C 2 -C 6 )alkanoyl, haloaiky!, or phenylCO-, phenylCH 2 CO-, phenyICH 2 CH 2 CO-, wherein the above phenyl groups are unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, (Ci-C 4 )alky!, (CI-C 4 ) alkoxy, nitro, CN, haloalkyl, haloalkoxy or CO 2 H; wherein the above alkyl groups are unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, methoxy, or ethox¥, R 2 is benzyloxy, phenethyloxy, phenpropyloxy, OH, phenyloxy, phenyloxy(Ci-C )alkyl, phenylthio(Ci-C 4 )alkoxy, NRsRg, (C 1 - C 6)alkyl, alkynyl, phenethyl, -OC(O)N(CH )CH 2 phenyI, alkoxyalkoxy, pyridyl, pyrimidyl, pyridazyl, pyrazolyl, imidazolyl, pyrrolyl, pyrazinyl, piperidinyl, hexahydropyrimidinyl, benzimidazolyl, or thienyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, -(CIC )alkyI-N(R)-CO 2 R 30, CF 3 , OCF (Ci-C 4 )alkyl, thienyl, pyridyl, or phenyl optionally substituted with i, 2, or 3 halogens; Re and Rv are independently at each occurrence H, (CIC ) alkyl, (CIC ) alkoxy, (CI-C ) alkoxy (CI-C 6 ) alkyl, (CI-C 6) alkoxycarbonyl, hydroxy (CI-C ) alkyl, - (CIC 4) alkyl-CO 2 -alkyl, (CI-C 6 ) alkanoyl, phenyl (CIC ) alkyl, phenyl (CI-C 6 ) alkoxy, or phenyl (CIC 6) alkanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, (Ci-C 6 )alk 0 xy, N'H 2 , OH, SH, C 3 -C cycloa!kyl, (C!-C )alkyl, CF 3 or OCFs; or R 6, R and the nitrogen to which they are attached form a morpholinyl, piperidiny!, pyrro!idinyl, or piperazinyi ring which is optionally substituted with 1 or 2 groups that are independently C:-C 4 alkyl, hydroxy, hydroxy C 2 -C 4 a!ky!, or halogen; is H, alkyl optionally substituted with one or two groups that are independently CO 2 H, -CO 2 aikyl, -C(O}NRR, N(R 0)C(O)NRR, -N(R 30 )C(O)-(C 1 -C 6 )alkoxy, or -NR R benzyloxy, phenethyloxy, phenpropyloxy, benzyl, phenethyl, phenpropyl, hydroxyalkyl, halo(C 1 -C )alkyl, carboxaldehyde, alkoxy, alkoxyalkyl, or alkoxyalkoxy, wherein the above phenyl groups are unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, CF 3 or OCF 3 ; and is benzyl, phenethyl, phenpropyl, phenbutyl, (C 1 -CG)alkyl, phenyl, piperidinyl, pyrrolidinyl, imidazolidinyl, piperidinyl (CI-C 6 ) alkyl, pyrrolidinyl (C 1 -C ) alkyl, imidazolidinyl(Ci-C 6)alky!, pyridyl, pyrimidyl, pyridazyl, pyrazinyl, pyridyl (CI-C 6 ) alkyl, pyrimidyl (CI-CG) alkyl, pyridazyl(Ci-C 6)alkyl, or pyrazinyl(C -C )alkyl wherein each of the above is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently alkyl, halogen, haloalkyl, NRsRg, NR 6 R -(CI-C alkyl)-, carboxaldehyde, morpholinyl, SO 2 NH 2 , SO 2 NH(alkyI), SO 2 N(alkyl) (alkyl), alkoxy, hydroxyalkyl, benzyloxy, thioalkoxy, OH, CO 2 H, CN, -CO (CI-Cs alkyl), phenylalkoxycarbonyl, amidinooxime, amidino, In this embodiment, it is methy! and Rs is phenyl, is preferred that when R 2 is OH, R R! is not acetyl. Embodiment A73. Compounds according to embodiment A72 wherein R! is halogen, alkyl, carboxaldehyde, hydroxy (C -C 4 ) alkyl, phenylalkoxy, benzyl, phenethyl, -C(O)CH 3 , phenylCO-, or phenyl CHACO-, wherein the above phenyl groups are unsubssituted or substituted with i, 2, or 3 groups that are independently halogen, (Ci-C 4 )alkyl, (C -C 4 ) alkoxy, nitro, CN, CF 3 , or OCF 3 ; wherein the above alkyl groups are unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, methoxy, or ethoxy; R 2 is benzyloxy, phenethyloxy, phenpropyloxy, OH, phenyloxy, phenyloxy(Q-CG)alkyl, phenethyl, N-R Rg, -S-benzy!, or (C 1 - C 6)alkyl, wherein each of the above is unsubstituted or substituted with l, 2, or 3 groups that are independently halogen, -(CIC 6)alkyI-N(R)-CO 2 R 30, CF 3 , OCF alkyl, thienyl, or pyridyl; R 6 and Rv are independently at each occurrence H, (CIC 6) alkyl, (CI-C 6 ) alkoxy, (CI-C 6 ) alkoxy (CI-C 6 ) alkyl, (CI-C ) alkoxycarbonyl, hydroxy (CI-C ) alkyl, - (CIC 4) alkyl-CO 2 -alkyl, (CI-C 6 ) alkanoyl, phenyl (CIC ) alkyl, phenyl (CI-C 6 ) alkoxy, or phenyl (C 1 - C 6)alkanoyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, (Ci-C 6 )alkoxy, NH 2 , OH, SH, C -C 6 cycloalkyl, (Ci-C )alkyl, CF or OCF ; RG, R and the nitrogen to which they are attached form a morpholiny!, piperidinyl, pyrrol idinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently C -C alkyi, hydroxy, hydroxy CI-C 4 alkyl, or halogen; R is H, alkyl optionally substltuned with one or two groups that are independently C0 2 H, -CO alkyl, -C (0) NRR N (Ra 0 ) C (O) NRR, -N(R 0 ) C (O) - (Ci-C 6 ) alkoxy, or -NR RT, benzyloxy, phenethyloxy, phenpropyloxy, benzyl, or hydroxyalkyl, wherein the above phenyl groups are unsubstituted or substituted with 1, 2, or 3 groups that are independent ly halogen, hydroxy, alkoxy, alkyl, nitro, CFa or OCF ; and Rs is benzyl, phenethyl, phenpropyl, phenbutyl, (CI-C 6 ) alkyl, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyrazinyl (C 1 - C 6)alkyl, pyrimidinyl(Ci-C 6 )alkyl, or pyridyl(Ci-C 4 )alkyl, wherein each of the above is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently alkyl, halogen, haloalkyl, morpholinyl, -SO 2 (CI-C 6 ) alkyl, -SO 2 NH -SO 2 NH (C 1 -C ) , -SO 2 N(CI-C 6 ) (C 1 -C ) , (CIC 4) alkoxy, phenyl (Cz-C 4 ) alkoxy, thio (CI-C 4 ) alkoxy, (CI-C 4) alkoxycarbonyl, OH, CO 2 H, CN, amidinooxime, amidino, NRsRg, NR Rv- (CI-C 6 alkyl) -, hydroxyalkyl, CONVERT, CF or OCF 3 . Embodiment A74. Compounds according to embodiment A73 wherein RI is halogen, alkyl, carboxaldehyde, or hydroxyalkyl; R 2 is benzyloxy, phenethyloxy, phenpropyloxy, OH, phenyloxy, phenyloxy(Ci-C 6)a!kyl, phenethyl, phenylthioalkoxy, or (Ci-C )alkyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, -(C - C ) alkyl-N (R) -CO 2 R 30 , CF 3 , OCF 3 , alkyl, hienvl, or pyridyl ; H, (CI-C 4 ) alkyl optionally substituted with one or two groups that are independently CO 2 H, -CO 2 a!kyl, -C(O)NFtR, -N (R 30 ) C (O) kLRR, -N (R 30 ) C (O) - (C -C ) alkoxy, or -NR 6 R benzyloxy, or phenethyloxy, wherein the above phenyl groups are unsubstituted or subssituted with I, 2, or 3 groups that are independent iy halogen, hydroxy, (Ci-C 4 )alkoxy, (Ci-C )alkyl, nitro, CF 3 or OCF 3 ; and is benzyl, phenethyl, (Ci-C 6 )alkyl, phenyl, indazolyl, or pyridyl, wherein each of the above is unsubstituted or substituted with 1, 2, 3, 4, or 5 groups that are independently (CI-C 4 ) alkyl, halogen, OH, CO 2 H, CN, (CI-C 4) alkoxy, -C (O) pyrrolidine, -SO 2 (CI-C 6 ) alkyl, benzyloxy, -CO 2 (CI-Cs alkyl) , amidino, thio(Ci-C 4 )alkoxy, amidinooxime, CF 3 , NRsRg, NR 6 R -(CI-C 6 alkyl) -, CONR 6 RT, or OCF Embodiment A75. Compounds according to embodiment A74 wherein chloro, bromo, iodo, methyl, C 2 -C 3 alkenyl, C 2 -C alkynyl; benzyl, phenethyl, phenpropyl, phenyl, or pyridyl, each of which is unsubstituted or substituted with i, 2, or 3 groups that are independently alkyl, OH, halogen, alkoxy, NH 2, NH(Q-C )alkyl, N(CI-C 6 )alkyl(C 1 -C 6 )alkyl, NRsRg, NR R - (C -C 6 alkyl)-, CONR Rv, and amidinooxime; wherein R and R are independently H, CI-C 4 alkyl, CI-C 6 alkanoyl, wherein the alkyl and alkanoyl groups are optionally substituted with I, 2, or 3 groups that are independen=!y OH, haiogen, or C 3 -C cyclopropy!. Embodiment A76. Compounds according to embodiment A75 wherein benzyloxy, phenethyl, pheny!oxy(C 1 -C )alkyi, or R 2 is phenethyloxy, each of which is unsubstituted or subsnituned with I, 2, or 3 groups that are independently halogen, -(CI-C )alkyI-N(R)-CO R 0 , CF 3 , OCF 3 , or (Ci-C 4 alkyl. Embodiment A77. Compounds according to embodiment A66, wherein R 5 is benzyl, phenethyl, thienyl (CI-C 6 alkyl) , piperidinyl (C 1 - C 6)alkyl, pyrrolidinyl (Ci-C 6 )alkyl, imidazolidinyl (C 1 - C 6)alky!, piperazinyl (CI-C 6 ) alky!, pyridyl (C 1 -C ) alkyl, pyrimidyl (CI-CG) alkyl, pyridazyl(C 1-C 6)alkyl, pyrazinyl(C 1 - isoquinolinyl (C 1 -C ) alkyl, CG) alkyl, tetrahydroisoquinoliny! (C 1 -C 6 ) alkyl, indolyl (C 1 -C 6 ) alkyl, or iH-indazolyl(C 1 -C 6 )alkyl, wherein each of the above is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently (C 1 - CG)alkyl, halogen, (C 1 -C 6 )alkoxy, (C 1 -C 6 )hydroxyalkyl, phenyl (Ci-C 6 ) alkoxy, (CI-C 6 ) thioalkoxy, (C 1 - CG) alkoxycarbonyl, phenyl (C 1 -C ) alkoxycarbonyl, OH, C0 2 H, CN, amidinooxime, NRsRg, NR 6 Rv- (CI-C 6 alkyl)-, - C (0) NR RT, amidino, piperazinyl, morpholinyl, -S0 2 (CI-C 6) alkyl, - S0 2 NH 2 , - S0 2 NH (CI-C 6 ) alkyl, -S0 2 N (CIC 6) alkyl (CI-C ) alkyl, (CI-C 4 ) haloalkyl, - (CI-C 4 alkyI)-NRIsC(O)NRI RIv, - (CI-C 4 alkyI)-NRIsC(O)R 18 , -OCH 2-O, -O-CH 2 CH 2 -O-, or (Ci-C 4 )haloalkoxy; wherein R and R are independently at each occurrence H, C 6) alkyl,( C - C 6 ) a I koxyca rbony!, ( CI - C ) hydroxya ! kyl,- (CI-Q)alkyl-CO 2 - (CI-C 6 )alkyl, (C -C 6) a!kanoyl, phenyl (CI-C ) alkyl, phenyl (C 1 - CG) alkoxy, or phenyl (CI-C ) alkanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, (C -C 4 )a!koxy, NH 2 , OH, SH, C 3 -C 6 cycloalkyl, N H (CI-C 6 alkyl) , N (CI-C alkyl) (CI-C 6 alkyl), (Ci-C 4 )alkyl, CF or OCF ; or R 6, RT, and the nitrogen to which they are attached form a morphol inyl, t hiomorphol inyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen; and R 18 is CI-C 6 alkyl optionally substituted with -O-(C 2 - C 6 alkanoyl, CI-C hydroxyalkyl, CI-C 6 alkoxy, CI-C 6 alkoxy CI-C 6 alkyl; amino CI-C 6 alkyl, mono or dialkylamino CI-C 6 alkyl. In this embodiment, it is preferred that R and Rv are not simultaneously OH; and RG and R are not simultaneously °SO 2 (CI-C 6 alkyl) . Embodiment A78. Compounds according to embodiment A77, wherein RI is halogen, methyl, ethyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, or carboxaldehyde; R 2 is benzyloxy, OH, phenyloxy, phenyloxy(Ci-C 6 )alkyl, or phenyl (CI-C 4 ) thioalkoxy, wherein each of the above is optionally substituted with !, 2, 3, or 4 groups that are independently halogen, -(CI-C 6 )alky!-N(R)-CO 2 R 0 , NR 6 RT, (CI-C 4) ha!oalky!, (Q-C 4 ) haloalkoxy, (Ci-C 6 ) a!kyl, or pyridyl ; and H, (C 1 -C ) alkyl optionally substituted with one or two groups that are independently C0 2 H, -CO a!ky!, -C(O)krRR, -N (R 30 ) C (O) NRR, -N (R 30 ) C (O) - (CI-C 6 ) alkoxy, or -k 6 R 7 , or hydroxy (CI-C 4 ) alkyl. Embodiment A79. Compounds according to embodiment A78, wherein benzyl, or phenethyl, wherein each is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently (CI-C 6 ) alkyl, halogen, (C 1 -C 6 ) alkoxy, (CIC 6) hydroxyalkyl, phenyl (CI-C ) alkoxy, (C!-C ) thioalkoxy, (C -C 6) alkoxycarbonyl, phenyl (CI-C 6 ) alkoxycarbonyl, OH, CO 2 H, CN, amidinooxime, NRsRg, NR 6 R - (Ci-C 6 alkyl) -, - C (O) NR R - (CI-C 4 alkyl) -C (O) NR 6 RTamidino, piperazinyl, morphol inyl, -SOs (Ci-C 6 ) a!kyl, -SO NH 2 , -SO 2 NH (CIC ) alkyl, -SO 2 N (C!-C 6 ) alkyl (CI-C 6 ) alkyl, (CI-C 4 ) haloalkyl, - (Q-C 4 alkyl-NRisC(O)R18, 18 , -O-CH 2 -O, -O-CH 2 CH 2 -O-, or (C 1 - C 4)haloalkoxy; wherein R 6 and R are independently at each occurrence H, (CiC 6) alkyl, (CI-C 6 ) alkoxy, (CI-C 6 ) alkoxy (Ci-C 6 ) alkyl, (C -C 6) alkoxycarbonyl, (C 1 -C ) hydroxyalkyl, - (C 1 - C 4)alkyl-CO 2-(C 1-C 6)alkyl, (C 1 -C 6 )alkanoyl, phenyl(C 1 ~ C ) alkyl, phenyl (CI-C 6 ) alkoxy, or phenyl (C 1 - C ) alkanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, (C 1 -C 4 )alkoxy, NH 2 , OH, SH, C 3 -C 6 cycloalky!, NH(C 1 -C 6 alkyl), N(CI-C 6 alkyl) (Ci-C 6 alkyl), (Ci-C 4 )alkyl, CF 3 or OCF 3 ; or R RT, and the nitrogen to which they are attached form a morphol inyl, t hiomorphol inyl, piperidinyl, pyrrol idinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently C!-C alkyl, hydroxy, hydroxy C.. -C alkyl, or halogen; and R e is CI-Ce alkyl optionally substituted with -O-(C=-Ce alkanoyl, CI-Ce hydroxyal kyl, C -Ce alkoxy, CI -Ce a!koxy CI-Ce alkyl, amino CI-C alkyl, or mono or dialky!amino CI-Ce alkyl. In this embodiment, it is preferred that R 6 and Rv are not simultaneously OH; and Re and R are not simultaneously -SO 2 (CI-C 6 alkyl) . Embodiment A80. Compounds according to embodiment A79, wherein is benzyl or phenethyl, wherein each is op=ionally substituted with I, 2, 3, 4, or 5 groups that are independently CI-C 6 alkyl,-C (O) NReRT. - (CI-C 4 alkyl ) - C(O)NReRT, NRsRg, halogen, C -Ce alkoxy, CO 2 H,- (CI-C 4 alkyl)-CO 2 H, CI-CG thioalkoxy, amidinooxime, Ci -C 6 alkoxycarbonyl 0 - (CI-C 4 a!kyl)-Ci-Ce alkoxycarbonyl, C -Ce hydroxyalkyl, - (CI-C 4 alkyl)-CN, CN, phenyl CI-C alkoxy, OH, CI-C 4 haloalkyl, CI-C 4 haloalkoxy, NR RT-(CI-C 6 alkyl)-, -(CI-C 4 alkyl-NRisC(O)R18, 18 , amidinooxime, -SO 2 (CI-C 6 alkyl), -O-CH 2-O-, -O-CH=CH 2 -O-, phenyl CI-C 4 alkoxy, or phenyl; wherein Re and R at each occurrence are independently H, OH, CI-C alkyl, amino CI-C 4 alkyl, NH(CI-Ce alkyl)alkyl, N(QC alkyl)(Ci-Ce alkyl) C 1 -Ce alkyl, CI-C 6 hydroxyalkyl, CI-C alkoxy CI-C alkyl, -SO 2 (CI-C 6 alkyl) each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -CG cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF or R 6, R and the nitrogen to which they are attached form a piperidinyl, pyrrolidiny!, piperaziny!, or a morpholinyl, thlomorpho!iny!, ring optionally substituted with i or 2 groups =hat are independently alkyl, hydroxy, hydroxy C 1 -C alkyl, or halogen, R 18 is CI-C 6 alkyl optionally substituted with -0-(C 2 -C 6 alkanoyl, Ci-C 6 hydroxyalkyl, C -C 6 alkoxy, C -C 6 al koxy Ci-C 6 alkyl ; amino C 1 -C alkyl, mono or dialkylamino CI-C 6 alkyl. this embodiment, it is preferred that R and R are not simultaneously OH; and and R 7 are not simultaneously -SO 2 (CI-C 6 alkyl) . Embodiment A81. Compounds according to embodiment A80, wherein is benzyl or phenethyl, wherein each is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C -C 6 a!kyl, -C (O) NR 6 RT, - (CI-C 4 alkyl ) - C(O)NR 6 Rv, halogen, CI-CG alkoxy, CO 2 H, -(CI-C 4 alkyl)-CO 2 H, C 1-CG thioalkoxy, amidinooxime, CI-C alkoxycarbonyl, -(CIC 4 alkyl)-C 1 -C alkoxycarbonyl, C 1 -C hydroxyalkyl, -(CI-C 4 alkyl)-CN, CN, phenyl C 1 -C alkoxy, OH, CI-C 4 haloalkyl, Ci-C 4 haloalkoxy, NR R - (Ci-C 6 alkyl) -, NRsRg, - (CI-C 4 alkyl)-NR 1 sC(O)R 18, amidinooxime, -SO=(CI-C alkyl) , -O-CH 2 - 0-, -O-CH 2 CH 2 -O-, phenyl CI-C 4 alkoxy, or phenyl; wherein R 6 and Rv at each occurrence are independently H, OH, CI-C alkyl, amino CI-C 4 alkyl, NH(CI-CG alkyl)alkyl, N(C 1 - C 6 alkyl)(CI-C alkyl) CI-C alkyl, CI-C 6 hydroxyalkyl, CI-C 6 alkoxy CI-C 6 alkyl, -SO 2 (CI-C alkyl) each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, Ci-C 4 alkoxy, C 1 -C 4 a!kyl, OH, CF 3 , or OCF 3 ; and RIB is CI-C 6 a!kyl optionally substituted with -O-(C=-C 6 alkanoyl, CI-C 6 hydroxyalkyl, C=-Ce al koxy, CI -C 6 alkoxy CI-Ce alkyl ; amino C--C 6 alkyl, mono or dialkylamino C=-C alkyl. In this embodiment, it is preferred that Re and Rv are not simultaneously OH; and Re and R are not simultaneously -SO 2 (CI-Ce alkyl) . Embodiment A82. Compounds according to embodiment A8!, wherein Rs is benzyl which is optionally substituted with I, 2, 3, 4, or 5 groups that are independently CI-C 4 alkyl, -C(O)NR 6 Rv. -(C:-C 4 alkyI)-C(O)NReR halogen, CI-C 4 alkoxy, CO 2 H, CI-C 4 thioalkoxy, CI-C 4 alkoxycarbonyl, CI-C hydroxyalkyl, CN, OH, NR 6 RT- (CI-Ce alkyl) - , NRsRg, -SOz (CI-C 6 alkyl) , or benzyloxy; wherein RG and R 7 at each occurrence are independently H, OH, CI-CG alkyl, amino CI-C 4 alkyl, NH(CI-Ce alkyl)alkyl, N(CICe alkyl)(CI-C 6 alkyl) CI-Ce alkyl, CI-Ce hydroxyalkyl, CI-C alkoxy CI-Ce alkyl, -SO 2 (CI-Ce alkyl) each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF 3 , or OCF 3. In this embodiment, it is preferred that R 6 and R 7 are not simultaneously OH; and RG and R are not simultaneously -SO 2 (CI-Ce alkyl). Embodiment A83. Compounds according to embodiment A82, wherein Rs is benzyl which is optionally substituted with i, 2, 3, 4, or 5 groups that are independently C:-C 4 alkyl, -C (O) NR 6 Rv. - (C!-C 4 alkyl) -C (O) krR 6 RT, halogen, Ci-C 4 alkoxy, C:-C 4 thioa!koxy, C 1 -C 4 alkoxycarbonyl, C:-C 6 hydroxyalky!, CN, NRsRg, or NR 6 R -(C:-C a!kyl)-; wherein R 6 and Rv at each occurrence are independent!i, H, OH, C:-C 6 alkyl, amino Ci-C 4 alkyl, NH(Ci-C 6 alkyi)a!kyl, N(C 1 - C 6 alkyl)(C 1 -C alkyl) C 1 -C alkyl, CI-C hydroxyalkyl, or Ci-C 4 alkoxy C:-C 4 alkyl each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, C 1-C 4 alkoxy, CI-C 4 alkyl, OH, CF 3 , or OCF 3 . In this embodiment, it is preferred that R 6 and Ro are not simultaneously OH. Embodiment A84. Compounds according to embodiment A83, wherein the Rs group is disubstituted with two groups that are meta to each other. Embodiment A86. Compounds according to embodiment A80, wherein R 5 is benzyl which is optionally substituted with i, 2, 3, 4, or 5 groups that are independently CI-C 4 alkyl, -C(O)NR 6 R ° -(CI-C 4 alkyI)-C(O)NR RT, NRsRg, NR 6 RT-(CI-C 6 alkyl)-, halogen, CI-C 4 alkoxy, CO 2 H, -(CI-C 4 alkyl)-CO 2 H, -(CI-C 4 alkyl)-Ci-C 6 alkoxycarbonyl, -(CI-C 4 alkyl)-CN, CN, phenyl CI-C 6 alkoxy, CF 3 , OCF 3 , -(C 1 -C 4 alkyI)-NRI C(O)R 18 , amidinooxime, -O-CH 2 -O-, -O-CH 2 CH 2 -O-, or phenyl; wherein R 6 and R 7 at each occurrence are independently H, CI-C 4 alkyl, amino CI-C 4 alkyl, NH(CI-C 4 alkyl)alkyl, N(CIC 4 alkyl)(CI-C 4 alkyl) CI-C 4 alkyl, CI-C 6 hydroxyalkyl, CI-C 4 alkoxy CI-C 4 alkyl, or OH, each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloa!kyl, CI-C 4 alkoxy, C -C 4 alkyl, OH, CF 3 , or OCF 3 ; and R 1 is C -C 6 alkyl, CI-C hydroxya!kyl, CI-C 6 alkoxy, C- -C 4 alkoxy C 1 -C alkyl ; amino CI -C 6 alkyl, mono or dialkylamino CI-C alkyl. In this embodiment, it is preferred that R 6 and R are not simultaneously OH. Embodiment A87. Compounds according to embodiment A80, wherein is benzyl or phenethyl, wherein each is optionally substituted with i, 2, 3 s 4, or 5 groups that are independently Ci-C 6 alkyl, -C(O)NR 6 R 7 . - (C -C 4 alkyl)- C(O)NR 6 Rv, halogen, C -C 6 alkoxy, CO 2 H, -(CI-C 4 alkyl)-CO 2 H, CI-C 6 thioalkoxy, amidinooxime, CI-C alkoxycarbonyl, -(C:- C 4 alkyl)-Ci-C 6 alkoxycarbonyl, CI-C hydroxya!kyl, -(CI-C 4 alkyl)-CN, CN, phenyl CI-C 6 alkoxy, OH, CI-C 4 haloalkyl, CI-C 4 haloalkoxy, NRsRg, NR 6 R - (CI-C 6 alkyl) -, - (CI-C 4 alkyI)-NRIsC(O)R 18, amidinooxime, -SO 2 (CI-C 6 alkyl), -O-CH 2 - O-, -O-CH 2 CH 2 -O-, phenyl CI-C 4 alkoxy, or phenyl ; wherein Re, R?, and the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, piperazinyl, or a morpholinyl, thiomorpholinyl, ring optionally substituted with 1 or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen, RIB is CI-C 6 alkyl optionally substituted with -O-(C 2 -C 6 alkanoyl, CI-C hydroxyalkyl, CI-C alkoxy, CI-C 6 al koxy CI-C alkyl ; amino CI -C 6 alkyl, mono or dialkylamino CI-C 6 alkyl. In this embodiment, it is' preferred that R 6 and R are not simultaneously OH; and Re and R 7 are not simultaneously -S0 2 (Ci-C 6 alky!). Compounds according to embodiment Embodiment A88. A87, wherein R 5 is ben=yl which is optionally substituted with I, 2, 3, 4, or 5 groups that are independently CI-C 4 alky!, -C(O)NR R -(C 1-C 4 alkyl)-C(O)NR 6 RT. halogen, Ci-C 4 a!koxy, CO 2 H, C 1 -C thioalkoxy, C:-C 4 alkoxycarbonyl, CI-C 6 hydroxyaikyl, CN, OH, NUMBER NR RT-(CI-C alkyl)-, -SO 2 (C!-C 6 alkyl , or benzyloxy; and wherein Re and R 7 at each occurrence are independently H, OH CI-C 6 alkyl, amino C 1 -C 4 alkyl, NH(C -C 6 alkyl)alkyl, N(C - C alkyl)(CI-C 6 alkyl) CI-C 6 alkyl, CI-C 6 hydroxyalkyl, CI-C 6 alkoxy CI-C 6 alkyl, or -SO 2 (CI-C 6 alkyl), each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 alkoxy, CI-C 4 aikyl, OH, CF 3 , or OCF]. In this embodiment, it is preferred that Re and Rv are not simultaneously OH; and R 6 and R 7 are not simultaneously -S0 2 (Ci-C 6 alkyl). Compounds according to embodiment Embodiment A89. A80, wherein Rs is benzyl which is optionally substituted with I, 2, 3, 4, or 5 groups that are independently CI-C 4 alkyl, -C (O) NRGRT 0 - (Ci-C 4 alkyl) -C (O) NR R ° NRGRT- (CI-C alkyl)-, NRsR 9 , halogen, Ci-C 4 alkoxy, Ci-C 4 thioalkoxy, CI-C 4 alkoxycarbonyl, CI-C hydroxyalkyl, or CN; wherein R 6 and Rv at each occurrence are independently H, OH, CI-C a!kyl, amino CI-C 4 alkyl, NH(CI-C 6 alkyl)alkyl, N(CIC alkyl)(CI-C alkyl) CI-C 6 alkyl, CI-C 6 hydroxyalkyl, or Ci-C 4 alkoxy Ci-C 4 alkyl, each of which is optionally substituted with I, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C cycloalkvl, CI-C 4 alkoxy, CI-C 4 a!kyl, OH, CF or OCF 3 . In this embodiment, it is preferred 5hat R 6 and R are not simultaneously OH. Embodiment A90. Compounds according to embodiment A89, wherein the Rs group is disubstituted with two groups that are me5a to each other. Embodiment Agl. Compounds according to embodiment A78, wherein Rs is phenyl, which is optionally substituted with i, 2, 3, 4, or 5 groups that are independently CI-C 4 alkyl, -C(O)NR RT, -NR 6 R NR 6 R (C!-C 6 alkyl) , NRsRg, CI-C 6 hydroxyalkyl, halogen, C -C 4 al koxy, CO 2 H, OH, Ci-C 6 al koxycarbonyl, carboxaldehyde, CI-C 4 haloalkyl, - (CI -C 4 alkyl ) - NRIsC(O)NRI 6 R 17, - (CI-C 4 alkyI)-NRIsC(O)RIB; wherein R and Rv at each occurrence are independently H, OH, C -C 6 alkyl, amino CI-C 4 alkyl, NH(CI-C 6 alkyl)alkyl, N(CIC alkyl)(CI-C alkyl) CI-C alkyl, CI-C hydroxyalkyl, CI-CG alkoxy CI-C alkyl, -SO 2 (CI-C 6 alkyl), -SO 2 NH 2 , -SO 2 NH(CI-C 6 alkyl), -SO 2 N(CI-C alkyl) (CI-C 6 alkyl), or CI-C 6 alkanoyl, each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C 6 cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF 3 , or OCF 3 ; or R 6, R and the nitrogen to which they are attached form a piperidinyl, pyrrol idinyl, piperazinyl, or a morpholinyl ring optionally substituted with 1 or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen, R 1 and R 17 are independently H or CI-C 6 alkyl; cr R 6, R , and the nitrogen to which they are attached form a morDholinv! ring; R 18 is CI-C 6 alky! optionally substituted with -O- (C:-C a! kanoyl, C:-C hydroxyal kyl, C - CG alkoxy, CI-C alkoxy C:-C alky! ; amino C:-C 6 alky!, mono or dialky!amino CI-C 6 alkyl. In this embodiment, it is preferred that R 6 and R are not simultaneously OH. Embodiment A92. Compounds according to embodiment Agl, wherein Rs is phenyl, which is optionally substituted with I, 2, 3, 4, or 5 groups that are independently CI-C 4 alkyl, -(CI-C 4 alkyl) -C (O) NEGRO -C (O) NR 6 RT, -NR 6 RT, NR 6 R 7 (Ci-C 6 alkyl) , krRsRg, CI-C 6 hydroxyalky!, halogen, C -C 4 alkoxy, CO 2 H, OH, C!-C 6 alkoxycarbonyl, carboxaldehyde, CI-C 4 haloalkyl, (Ci-C 4 alkyl)-NR 15 C (0) NR 6 RI - (Ci-C 4 alkyl)-NR 15 C (O) R 18 ; wherein R 6 and R at each occurrence are independently H, OH, CI-C 6 alkyl, amino CI-C 4 alkyl, NH(CI-C 6 alkyl)alkyl, N(C 1 - C 6 alkyl)(CI-C 6 alkyl) CI-C 6 alkyl, C 1 -CG hydroxyalkyl, Ci-C 6 alkoxy CI-C 6 alkyl, -SO 2 (CI-CG alkyl), -S0 2 NH 2 , -S0 2 NH(CI-C 6 alkyl), -SO 2 N(CI-C alkyl) (CI-C 6 alkyl), or CI-C 6 alkanoyl each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C cycloalkyl, CI-C 4 alkoxy, CI-C 4 alkyl, OH, CF or OCF ; R is H or C -C alkyl; R 6 and R v are independently H or C -C alkyl; or R R and the nitrogen to which they are attached form a morpholinyl ring; R 18 is Ci-C 6 a!kyl optionally substituted with -0- (C 2 -C 6 alkanoyl, CI-C 6 hydroxyalkyl, CI-C 6 alkoxy, C!-C 6 alkoxy Cz-C 6 alkyl ; amino CI-C 6 a!kyl, mono or dialkylamino CI-C 6 alkyl. Embodiment A93. Compounds according to embodiment A92, wherein halogen, methyl, ethyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, or carboxaldehyde ; is benzyloxy, OH, phenyloxy, phenyloxy (C 1 -C ) a!kyl, or phenyl (CI-C 4 ) thioalkoxy, wherein each of the above is optionally substituted with I, 2, 3, or 4 groups that are independently halogen, - (CI-C ) alkyl-N (R) -C0 2 R 30 , NR 6 RT, (C -C 4) haloalkyl, (CI-C 4 ) haloalkoxy, (C 1 -C ) alkyl, pyridyl, or NRGRT- (CI-C 6 alkyl)-; and H, (CI-C 4 ) alkyl optionally substituted with one or two groups that are independently C0 2 H, -C0 2 alkyl, -C(O)NRR, - N (R 30 ) C (0) NRR, -N (R 30 ) C(O) - (CI-C 6 ) alkoxy, or -NR RT, or hydroxy (C 1 - C 4 ) al kyl. Embodiment A94. Compounds according to embodiment A93, wherein phenyl, which is optionally substituted with i, 2, 3, 4, or 5 groups that are independently CI-C 4 alkyl, -C(O)NR Rv, -(CI-C 4 alkyI)-C(O)NR 6 R -NR 6 R NR 6 Rv(CI-C 6 alkyl) , CI-CG hyd roxya i kyl, ha 1 ogen, CI - C 4 al koxy, CO 2 H, OH, CI - C alkoxycarbonyl, carboxaldehyde, C -C 4 haloalkyl, wherein R and R 7 at each occurrence are independently H, OH, CI-C alkyl, amino CI-C 4 alkyl, NH(CI-C 6 alkyl)alkyl, N(CIC 6 alkyl) (CI-C 6 alkyl) CI-CG alkyl, CI-C 6 hydroxyalkyl, CI-CG alkoxy CI-C 6 alkyl, -SO 2 (CI-C alkyl), -SO 2 NH 2 , -S0 2 NH(CI-C 6 alkyl), -S0 2 N(CI-C 6 alkyl) (CI-C alkyl), or CI-C 6 alkanoyl, each of which is optionally substituted with i, 2, or 3 groups that are independently halogen, OH, SH, C 3 -C cycloalkyl, C -C 4 alkoxy, C -C 4 aikyl, OH, CF 3 , or OCF 3 ;. Embodiment AI01. Compounds according to embodiment A66, wherein is thienyl(C -C 6 a]kyl), piperidinyl (C 1 -C ) alkyl, pyrrolidinyl(Ci-C 6)alky!, imidazolidiny! (C 1 -C ) alkyl, piperazinyl(C 1-C )alkyl, pyridyl(C 1 -C )alkyl, pyrimidyl(C 1 - C ) alkyl, pyridazyl (CI-C 6 ) alkyl, pyrazinyl (C 1 -C ) alkyl, isoquinolinyl (C 1 -C 6 ) alkyl, tetrahydroisoquinolinyl(C 1C 6] alkyl, indolyl (Ci-C 6 ) alkyl, iH-indazolyl(Ci-C alkyl, dihydroindolonyl (C 2 -C alkyl) , indo!inyl(C 1-C 6 alkyl), dihydroisoindoly! (CI-C 6 alkyl) , dihydrobenzimdazoly!(C 1-C 6 alkyl), or dihydrobenzoimidazolonyl(C 1 -C 6 alkyl), wherein each of the above is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently (CI- C 6 }alkyl, halogen, (C 1 -C 6 }alkoxy, (C 1 -C 6 )hydroxyalkyl, phenyl (Ci-C 6 )alkoxy, (C 1 -C ) thioalkoxy, (CiC 6) alkoxycarbonyl, phenyl (C 1 -C 6 ) alkoxycarbonyl, OH, C0 2 H, CN, amidinooxime, NRsRg, NR 6 Rv- (C 1 -C alkyl) ~, C (0) Nervous, - (CI-C 4 alkyl) -C (0) NR 6 Rv 0 amidino, piperazinyl, morpholinyl, -S0 2 (CI-C 6 ) alkyl, -S0 2 NH 2 , -SO NH (Q-C 6 ) alkyl, -SO 2 N (C 1 -C 6 ) alkyl (C -C 6 ) alkyl, (C 1-C 4)haloalkyl, -(Ci-C 4 alkyI)-NRIsC(O)NRI 6 R 17 , -(CiC 4 alkyl-NRIsC(O)R18, 18 , -O-CH 2 -O, -O-CH 2 CH 2 -O-, or (C 1 - C 4)haloalkoxy; wherein R and Rv are independently at each occurrence H, (Ci-C 6) alkyl,(Ci-C 6) alkoxy, (Ci-C 6 ) alkoxy (C 1 - C 6) alkyl,(C -C ) alkoxycarbonyl, (C - C ) hydroxya i kyl,- (C -C ) alkyl-CO - (C -C ) alkyl, (Ci-C 6) alkanoyl, phenyl (CI-C ) alky!, phenyl (C 1 - C 6) alkoxy, or phenyl (e 1 -c 6 ) alkanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, (C: -C 4 ) alkoxy, OH, SH, C 3-C cycloalkyl, NH 2 , N '(CI-C alky!) , N(CI-C 6 alkyl) (C 1 -C alkyl), (C -C 4 )a!kyl, CF 3 or OCF ; or R 6, R and the nitrogen to which they are attached form a morphol inyl, t hiomorphol inyl, piperidiny!, pyrrolidinyl, or piperaziny! ring which is optionally substituted with 1 or 2 groups that are independently C 1 -C 4 alkyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen; and R 18 is C:-C a!kyl optionally substituted with -O-(C 2 - C 6 alkanoyl, C -C 6 hydroxyalkyl, C 1 -C 6 alkoxy, CI-C 6 alkoxy Ci-C 6 alkyl; amino Ci-C 6 alkyl, mono or dialkylamino C -C 6 alkyl. In this embodiment, it is preferred that R 6 and Rv are not simultaneously OH; and R 6 and Rv are not simultaneously -SO 2 (CI-C alkyl) . Embodiment A102. Compounds according to embodiment AI01, wherein RI is halogen, methyl, ethyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, or carboxal dehyde ; R 2 is benzyloxy, OH, phenyloxy, phenyloxy (CI-C 6 ) alkyl, or phenyl (CI-C 4 ) thioalkoxy, wherein each of the above is optionally substituted with i, 2, 3, or 4 groups that are independently halogen, - (Q-C 6 ) alkyl-N (R) -CO,R 30 , NKGRT, (C -C 4) haloalkyl, (C -C 4 ) haloalkoxy, (C -C 6 ) alkyl, pyridyl, or NR 6 RT-(CI-C alkyl)-; and H, (C--C 4 ) alkyl optionally substituted with one or two groups that are independently C0 2 H, -CO 2 alkyl, -C(O)NRR, -N(R 30)C(O)NRR, -N(R 30 )C(O)- (C 1 -C 6 )aikoxy, or -NR RT, or hydroxy ( C i - C 4 ) a I kyl . Embodiment AI03. Compounds according to embodiment AI02, wherein thieny!(C 1 -C 6 a!kyl), indoly!(C 1 -C 6 a!ky!), pyridinyi(C 1 -C 6 alkyl), piperazinyl(C 1 -C alky!), or pyrazinyl(C 1 -C 6 alkyl) each of which is optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkyl, CI-C 4 hydroxya!kyl, halogen, -C (O) NR RT, - (C!-C 4 a!kyl)-C(O)NR RT. Ci-C 6 alkoxycarbonyl, -NR 6 R NRGRT- (Ci-C 6 alkyl) -, haloalkyl, CI-C 6 alkanoyl, R 6 and R at each occurrence are independently H, CI-C alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C -C 6 cycloalkyl, OH, SH, or C -C alkoxy; or R 6, R and the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, piperazinyl, or a morpholinyl ring optionally substituted with 1 or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment AI04. Compounds according to embodiment AI03, wherein thienyl(Ci-C alkyl), indolyl(Ci-C alkyl), pyridinyl(Ci-C 6 alkyl), piperazinyl(Ci-CG alkyl), or pyrazinyl(Ci-C alkyl). Embodiment AI05. Compounds according to embodiment A!03, wherein H, methyl, ethyl, or -CH OH; pyridinyl(C 1 -C 6 alkyl), or pyrazinyl(C 1 -Ce alkyl) each of which is optionally substituted with !, 2, or 3 groups that are independently C 1 -C alkyl, C -C 4 hydroxyalkyl, halogen, -C (O) NR R - (C:-C alkyl) -C (O) NR RT. C 1 -C alkoxycarbonyl, -NReR NR RT- (CI-C a!kyl) -, CF CI-Ce alkanoy!, wherein Re and R at each occurrence are independently H, CI-C 6 alkyl optionally substituted with I, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3-C cycloalkyl, OH, SH, or CI-C 4 alkoxy; or Re, RT, and the nitrogen to which they are attached form a piperidinyl, pyrro!idinyl, piperaziny!, or a morpholinyl ring optionally substituted with 1 or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment AI06. Compounds according to embodiment AI05, wherein is H, alkyl substituted with one or two groups that are independently CO 2 H, -CO 2 -(Q-Ce)alkyl, -C(O)NRR, -N(R 30)C(O)NRR, -N(R 30 )C(O)-(C 1 -Ce)alkoxy, or -NReRT. Embodiment All2. Compounds according to embodiment 16, wherein halogen, or methyl; benzyloxy, which is optionally substituted with i, 2, 3, or 4 groups that are independently halogen, -(CI-C )alkyIN(R)-CO 2 R 0, CF 3 , OCF 3 , or (Ci-C 4 ) alkyl, ; and is H, methyl, ethyl, -CH 2 OH, -CH 2 CO 2 -(CI-C 4 alkyl) , or C 2 hydroxyalkyl. Embodiment A!I3. Compounds according to any one of embodimenZs A85, A95, A97, A98, A99, AI00, 16 or 17, wherein Ri is halogen, or methyl; R 2 is benzyloxy, which is omtional!y substituted with i, 2, 3, or 4 groups that are independently halogen, -(C.-C 6 )alkyIN(R)-CO 2 R 30, CF 3 , OCF 3 , or (CI-C ) a!ky!,; and R 4 is alkyl substituted with one group that is CO H, -C0 2 -(C 1 - C 6)alkyl, -C(O)NRR, -N(Ra 0 )C(O)N.-RR, -N(R] 0 )C(O)- (CI- C 6 )alkoxy, or -NR 6 RT. Embodiment All4. Compounds according to embodiment A66, wherein Rs is isoquinolinyl(C 1 -C 6 alkyl), tetrahydroisoquinolinyl(C 1 -C a!kyl) IH-indazo!yl (C 1 -C alkyl) , dihydroindolonyl (CI-C 6 alkyl) indolinyl (Ci-C 6 alkyl) , dihydroisoindolyl (C 1 -C 6 alkyl) , dihydrobenzimdazolyl (Ci-C 6 alkyl ) , dihydrobenzoimidazolony! (CI-C 6 alky!) , each of which is unsubstituted or substituted with i, 2, or 3 groups that are independently alkyl, alkoxy, halogen, C 1 -C alkoxycarbonyl, alkanoyl optionally substituted with 1 or 2 groups that are independently selected from the group consisting of OH, N-H 2 , NH(CI-C 6 alkyl), and N(C 1 -C alkyl) (CI-CG alkyl), -C (O) NR 6 Rv, -(CI-C 4 alkyl)-C(O)NR 6 RT, NR 6 RT- (C 1-C alkyl-, -NR 6 RT, or S0 2 H; or piperidinyl C 1 -C 4 alkyl optionally substituted with I, 2, or 3 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, halogen, -C(O)NR 6 Rv, -(C 1 -C 4 alkyl)-C(O)NR 6 Rv 0 NR 6 RT-(CI-CG alkyl)-, or -NR 6 RT, or CI-C 6 alkoxycarbonyl. Embodiment AI!5. Compounds according to embodiment All4, wherein is isoquinolinyl(Q-C 4 alkyl), piperidinyl Ci-C 4 alkyl, tetrahydroisoquinoliny!(C 1-C 4 alkyl),!H-indazolyl(C=-C 4 a!kyl), dihydroindolonyl(C 1 -C 4 a!kyl), indo!inyl(C=-C 4 alkyl), dihydroisoindolyl(C 1 -C 4 alkyl), dihydrobenzimdazolyl(C:-C 4 a!kyl), or dihydrobenzoimidazolonyl(C 1-C 4 alky!) . Embodiment All6. Compounds according to embodiment All4, wherein piperidinyl C:-C 4 alkyl optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, halogen, or C 1 -C alkoxycarbonyl. Embodiment All7. Compounds according to embodiment A66, wherein is pyrimidyl, indolinyl, indolyl, iH-isoindolyl, isoquinolinyl, tetrahydroisoquinolinyl, benzimidazolyl, dihydro-IH-benzimidazolyl, pyrrclyl, imidazolyl, or each of which is optionally substituted with I, 2, or 3 groups independently selected from the group consisting of CI-C alkoxycarbonyl, CI-C 4 thioalkoxy, each of which is unsubstituted or substituted with i, 2, or 3 groups that are independently -C(O)NR 6 Rv, -(CI-C 4 alkyl)- C(O)NRGRv° NR 6 Rv-(CI-C alkyl)-, -NR 6 R alkyl, alkoxy, halogen, CI-C alkoxycarbonyl, or alkanoyl optionally substituted with 1 or 2 groups that are independently selected from the group consisting of OH, NH 2 , NH(CI-C 6 alkyl), and N(CI-C 6 alkyl) (CI-C 6 alkyl), and SO 2 H; or pyridyl, pyrazolyl, optionally substituted with i, 2, or 3 groups that are independently -C(O)NR 6 R -(CI-C 4 alkyl)-C(O)NR R NR R -(CI-C alkyl)-, -NRGR CI-C 4 alkyl 0 Ci-C 4 hydroxyalkyl, halogen, Ci-C 6 alkoxycarbonyl, -NR 6 RT, NR 6 R:- (Ci-C 6 alkyl-, CF C 1 - C 6 alkanoy!, wherein R 6 and R: at each occurrence are independently H, C - C 6 alkyl optionally substituted with i, 2, or 3 groups that are indeoendentlv C -C alkoxycarbonyl, halogen, C 3 -C 6 cyc!oalky!, OH, SH, or CI-C alkoxy; or R 6, RT, and the nitrogen to which they are attached form a piperidinyl, pyrrolidiny!, piperazinyl, or a morpholinyl ring optionally substituted with i or 2 groups that are independently alkyl, hydroxy, hydroxy CI-C 4 aikyl, or halogen. Embodiment AIIS. Compounds according to embodiment AI!7, wherein pyrimidyl, pyrrolyl, imidazolyl, or pyrazolyl, each of which is optionally substituted with i, 2, or 3 groups independently selected from CI-C 6 alkoxycarbonyl, CI-C 4 thioalkoxy, each of which is unsubstituted or substituted with I, 2, or 3 groups that are independently alkyl, alkoxy, halogen, CI-C alkoxycarbonyl, -C(O)NR Rv, -(CI-C 4 alkyl)-C(O)NR 6 Rv, NR 6 RT-(CI-C 6 alkyl)-, or NR 6 Rv, or CI-C 4 alkanoyl optionally substituted with 1 or 2 groups that are independently selected from the group consisting of OH, NH 2 , NH(CI-C 6 alkyl), and N(CI-C 6 alkyl) (C -C 6 alkyl), or SO 2 H. Embodiment All9. Compounds according to embodiment All7, wherein is pyridyl or pyrazolyl, optionally substituted with I, 2, or 3 groups that are independently C -C 4 alkyl, CI-C 4 hydroxyalkyl, halogen, -C(O}NR 6 R -(C -C 4 alkyI)-C(O)NR 6 R NR 6 RT°(CI-C alkyl)-, or -NR RT, C 1 -C alkoxycarbonyl, - NR Rv, NR 6 R -(CI-C alkyl-, CF 3 , Zi-C 6 alkanoyl, wherein R 6 and R 7 at each occurrence are independently H, C=-C 6 a!kyl optionally substituted with !, 2, or 3 groups that are independently C:-C 4 a!koxycarbonyl, halogen, C 3-C cycloaikyl, OH, SH, or CI-C 4 a!koxy; or Re, R and the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, piperazinyl, or a morpholiny! ring optionally substituted with i or 2 groups that are independently alkyl, hydroxy, hydroxy Ci-C 4 alkyl, or halogen. Embodiment AI20. Compounds according to embodiment All9, wherein is pyridyl or pyrazolyl, optionally substituted with I, 2, or 3 groups that are independently CI-C 4 alkyl, CI-C 4 hydroxyalkyl, halogen, -C (O) NR 6 R - (CI-C 4 alkyI)-C(O)NR 6 RT. NR 6 R - (CI-C 6 alkyl)-, -NR 6 RT, CI-C 6 alkoxycarbonyl, CF CI- C 6 alkanoyl, wherein and Rv at each occurrence are independently H, CI-C alkyl optionally substituted with I, 2, or 3 groups that are independently CI-C 4 alkoxycarbonyl, halogen, C 3 -C cycloalkyl, OH, SH, or CI-C 4 alkoxy. Embodiment AI21. Compounds according to embodiment AIIg, wherein pyridyl or pyrazolyl, optionally substituted with i, 2, or 3 groups that are independently CI-C 4 alkyl, CI-C 4 hydroxyalkyl, halogen, -C(O)N'R 6 Rv, -(CI-C 4 alkyl)-C(O)NR R NRGR -(CI-CG alkyl)-, -NR Rv, CI-C 6 alkoxycarbonyl, CF 3 , CIC alkanoyl, wherein R 6, R and the nitrogen to which they are attached form a piperidinyl, pyrrolidiny!, plperaziny!, or a morphoiinyl ring optionally substituted with 1 or 2 groups that are independently alkyl, hydroxy, hydroxy C 1 -C 4 alky!, or halogen. Embodiment A122. Compounds according to any one of embodiments All4, AI!5, All6, or All7 wherein R! is halogen, methyl, ethyl, C 2 -C 4 alkenyi, C 2 -C 4 alkynyl, or carboxaldehyde ; R 2 is benzyloxy, OH, phenyloxy, phenyloxy (C 1 -C ) alkyl, or phenyl (CI-C 4 ) thioaikoxy, wherein each of the above is optionally substituted with i, 2, 3, or 4 groups that are independently halogen, - (C 1 -C 6 ) alkyl-N (R) -C0 2 R 30 , NR 6 Rv, (C 1-C 4) haloalkyl, (CI-C 4 ) haloalkoxy, (CI-C 6 ) alkyl, pyridyl, or Nqg RT- (C 1 -C alkyl)-; and R 4 is H, (C!-C 4 ) alkyl substituted with one group that is CO 2 H, -CO 2- (C 1 -C )alkyl, -C(O)NRR, -N(R 30 )C(O)NRR, -N(R 30 )C(O)- (C 1-C 6)alkoxy, or -NR 6 RT, hydroxy(C 1 -C 4 )alkyl. Embodiment A123. Compounds according to embodiment A66, wherein Rs is CI-C alkyl optionally substituted with 1 or 2, groups that are independently CI-C 4 alkoxycarbonyl, or halogen, or Rs is CI-C 4 alkoxy, ethyl, methyl, cyclopropylmethyl, cycloalkyl, or alkynyl, or Rs is C -C 6 alkenyl optionally substituted with CI-C 4 alkoxycarbonyl or cyclohexyl. Embodiment A124. Compounds according to embodiment A123, wherein halogen, methyl, ethyl, C -C 4 alkenyl, C 2 -C a!kyny!, or carboxaldehyde ; is benzy!oxy, OH, phenyloxy, phenyloxy (CI-C 6 ) alkyl, or phenyl (CI-C 4 ) thioalkoxy, wherein each of the above is optionally substituted with I, 2, 3, or 4 groups that are independently halogen, - (C:-C ) alkyl-N (R) -CO,R 30 , NR 6 R (CI-C 4) haloalkyl, (CI-C 4 ) haloalkoxy, (C!-C 6 ) alkyl, pyridyl, or NR 6 RT- (CI-C 6 alkyl)-; and H, (CI-C 4 ) alkyl substituted with one group that is CO 2 H, -C0 2- (C 1 -C 6 ) alkyl, -C (O)NRR, -N (R 0 ) C (0) NRR, -N (R 30 ) C (O) - (Ci-C 6)alkoxy, or -NR 6 R hydroxy(C -C 4 )alkyl; wherein R 6 and Rv at each occurrence are independently H, CI-C 6 alkyl optionally substituted with i, 2, or 3 groups that are independently C -C 4 aikoxycarbonyl, halogen, C -C cycloalkyl, OH, SH, or C:-C 4 alkoxy; or R R and the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, piperazinyl, or a morpholinyl ring optionally substituted with 1 or 2 groups that are independently alkyl, hydroxy, hydroxy Ci-C 4 alkyl, or halogen. Embodiment A125. Compounds according to embodiment A124, wherein is CI-C alkyl optionally substituted with 1 or 2, groups that are independently CI-C 4 alkoxycarbonyl, or halogen, or is CI-C 4 alkoxy, ethyl, methyl, cyclopropylmethyl, cyclohexyl, cyclopentyl, C 2 -C 6 alkynyl, or is C 2 -C alkenyl optionally substituted with CI-C 4 alkoxycarbonyl or cyclohexyl. Embodiment A126. Compounds according to embodiment wherein is phenyla!kynyl, -OC (0) NH (CH=) naryl, -OC (O) N (alkyl) (CH ) naryl, -0SO 2 (C!-C ) alkyl, -OS0 2 ary!, or NRERg, wherein n is 0, I, 2, 3, 4, 5 or 6; each of the above is unsubstituted or substituted with !, 2, 3, 4, or 5 groups that are independently halogen, -(C 1-C 6)alkyI-N(R)-CO 2 R 30, a!koxy, alkoxycarbonyl, CN, NR 6 RT, haloalkyl, haloalkoxy, alkyl, heteroaryl, heteroarylalkyl, NR R -(CI-C 6 alkyl)-, phenyl, -SO 2 - phenyl wherein the phenyl groups are optionally substituted with I, 2, or 3 groups that are independently halogen or NO 2 ; or -OC(O)NR R wherein Re and Rv are independently at each occurrence H, alkyl, alkoxy, a!koxya!kyl, alkoxycarbonyl, S0 2-alkyl, OH, hydroxyalkyl, -(Q-C )alkyl-CO 2 - alkyl, heteroarylalkyl, alkanoyl, arylalkyl, arylalkoxy, or arylalkanoyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, alkoxy, heterocycloalkyl, OH, NH 2 , CaC cycloalkyl, NH(alkyl), N(alkyl) (alkyl), -Oalkanoyl, alkyl, CI-C 4 haloalkyl, or CI-C 4 haloalkoxy; or R RT, and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment A127. Compounds according to embodiment wherein halogen, methyl, ethyl, C -C 4 alkenyl, C 2 -C 4 alkynyl, or carboxaldehyde; and H, (C -C 4 ) alkyl substituted with one group that is CO 2 H, -C0 2- (C 1 -C 6 )alkyl, -C(O)NRR, -N(R 30 )C(O)NRR, -N(R 30 )C(O)- (Ci-C )alkoxy, -NR RT, NR 6 R -(CI-C 6 alkyl)-, or hydroxy(C 1 - C 4 ) alkyl. Embodiment A128. Compounds according to embodiment wherein phenyl, optionally substituted with I, 2, 3, 4, or groups that are independently halogen, CI-C 4 alkyl, CI-C 4 alkoxy, CF 3 , OCF -(CI-C 4 alkyI)-C(O)NR 6 R NR 6 RT-(CI-CG alkyl)-, -NR Rv, or C(O)NR 6 Rv, wherein R 6 and R are independently at each occurrence H, CI-C alkyl, CI-C 6 alkoxy, CI-CG alkoxy CI-C 6 alkyl, CI-C alkoxycarbony!, OH, Ci-C 6 hydroxyalkyl, - (CIC 4) alkyl-CO 2 -alkyl, pyridyl Ci-C 6 alkyl, CI-C 6 alkanoyl, benzyl, phenyl CI-C 6 alkoxy, or phenyl CIC 6 alkanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, CI-C alkoxy, piperidinyl C -C 6 alkyl, morphol inyl CI-C 6 alkyl, piperazinyl CI-C 6 alkyl, OH, SH, C 3 -C 6 cycloalkyl, NH 2, NH(alkyl), N(alkyl) (alkyl), -O-C 1 -C 4 alkanoyl, CI-C 4 alkyl, CF 3 , or OCF 3 ; or Re, R and the nitrogen to which they are attached form a morphol inyl, t hiomorphol inyl, piperidinyl, pyrrol idinyl, or pipera zinyl ring which is optionally substituted with 1 or 2 groups that are independently C -C 4 alkyl, C -C 4 al koxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen; or is benzyl optionally substituted with I ,2 ,3 ,4, or groups that are independently halogen, C=-C 6 a!kv!, CI-C alkoxy, CN, CF 3 , OCF 3 , -(C 1 -C alkyi)-C(O)NR RT. NR R -(C=-C 6 alky!)-, -NR 6 Rv, or C(O)NR R Embodiment A129. Compounds according to embodiment A!28, wherein NRaRg, or N-RsR -(C:-C aikyl)-; wherein R 8 at each occurrence is independently hydrogen, C -C 6 alkyl, C -C 6 alkanoyl, phenyl(Q-C )alkyl or phenyl(C 1-C 6)aikanoyl wherein each of the above is optionally substituted with i, 2, 3, 4, or 5 groups that are independently CI-C 6 alkyl, CI-C 6 alkoxy, CIC 6 alkoxycarbonyl, halogen, or CI-C 4 haloalky!; and R 9 at each occurrence is independently CI-C alkyl, CI-C 6 alkanoyl, phenyl(C 1 -C 6 )alky!, C 3 -C cycloalkyl, C 2 -C 6 alkenyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, imidazolyl, C 3 -C cycloalkyl(C 1 -C 6 )alkyl, phenyl(C 1-C 6)alkanoyl, -SO -phenyl, and phenyl wherein each of the above is optionally substituted with I, 2, 3, 4, or 5 groups that are independently CI-C alkyl, CI-C alkoxy, CI-C alkoxycarbonyl, ha!ogen, or CI-C 4 haloalkyl. Embodiment AI30. Compounds according to embodiment A129, wherein H. Embodiment AI31. Compounds according to embodiment AI30, wherein -NH-benzyl option substituted with i, 2, or 3 groups that are independently halogen, CI-C 4 alkyl, CI-C 4 alkoxy, CF 3 , is -NH-C(O)phenyl, wherein the phenyl group is op%ionally substituted with i, 2, or 3 groups that are independently halogen, CI-C 4 alkyl, or CI-C 4 a!koxy; or is -NH-allyl. Embodiment A132. Compounds according to embodiment AI31, wherein is chloro, bromo, iodo, or methyl; and is benzyl optionally substituted with 1 ,2 ,3 ,4, or groups that are independently halogen, -(C -C alkyI)- C(O)NR 6 R NR 6 R -(CI-C 6 alkyl)-, -N-R 6 Rv, CI-C 6 alkyl, CI-C 6 alkoxy, CN, CF 3 , OCF 3 , or C(O)NR 6 RT. Embodiment A133. Compounds according to embodiment AI31, wherein is chloro, bromo, iodo, or methyl; and is phenyl, optionally substituted with i, 2, 3, 4, or groups that are independently halogen, -(C -C 4 alkyI)- C(O)NR 6 R NR 6 R -(CI-C 6 alkyl)-, -NR 6 R CI-C 4 alkyl, CI-C 4 alkoxy, CF OCF 3 , or C(O)NR RT. Embodiment A134. A compound of the formula H Y X 2 y- ' 1 Y 2 X 1" "NO I Rs pharmaceutically acceptable salts thereof, wherein I R 5 is Xc or Xc ; wherein 2 , Xa, Xb, X=, Xd, and Xe at are independently selected from -C (O) NR R -NR 6 R hydroxy (Q-C ) a!ky!, H, OH, halogen, haloa!kyl, alkyl, haloalkoxy, heteroaryl, heterocycloalkyl, C 3 -C cycloalky!, NR 6 R -(C 1 -C a!kyl)-, C0 2- (CI-C 6 ) alkyl, -N (R) C(O) NR 6 R -N(R) C(O)- (CI-C ) a!koxy, CO 2 H- {C 1 -C alkyl) -, or -SO NR 6 R ; wherein the heteroaryl and heterocycloalky! groups are optionally substituted with -NR 6 R=, -C(O)A,-R RT, NR 6 R - (C 1 -C alkyl) -, C 1-CG alkyl, Ci~C 6 alkoxy, or halogen; R 6 and R 7 are independently at each occurrence H, CI-C aikyl, CI-C 6 alkoxy, C 1 -C 6 alkoxy C 1 -C 6 a!ky!, C 1 -C alkoxycarbonyl, OH, C -C 6 hydroxyal kyl, C 1 -C thiohydroxyalkyl, - (CI-C 4 alkyl-CO=-alkyl, pyridyl CIC 6 alkyl, C -C alkanoyl, benzyl, phenyl CI-C 6 alkoxy, or phenyl CI-C 6 alkanoyl wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, C -C 6 cycloalkyl, CI-C 6 alkoxy, piperidinyl CI-C 6 alkyl, morpholinyl CI-C alkyl, piperazinyl CI-C 6 alkyl, OH, SH, NH 2 , NH (alkyl) , N (alkyl) (alkyl) , -0-C -C 4 alkanoyl, CI-C 4 alkyl, CF 3 , or OCF ; or R RT, and the nitrogen to which they are attached form a mo rpho i inyl, thiomorphol inyl, pipe ridinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C alkyl, or halogen; R at each occurrence is independently H or C -C 6 a!kyl; and Y 1, Yz, Y 3 , and Y are independently selected from H, Y, halogen, alkyl r carooxa±dehyd • e , hydroxya!ky! , a!kenvl . t alkynyl, CN, a!kanoyl, alkoxy, alkoxyalky!, haloalkyl, and carboxyl. to embodiment Embodiment A135. Compounds according A134, wherein Y 2, Y 4 , and Y are independently halogen; and Y and Y 3 are both hydrogen. Embodiment A136. Compounds according to embodiment A135, wherein Xz is H, methy!, -NR RT, NR 6 Rv-(C -C 6 alkyl)-, -C(O)NR 6 RT, Cz-C hydroxyalkyl, or -(CI-C 4 alkyl)-morpholinyl. Embodiment A137. Compounds according to embodiment A136, wherein Xa and Xe are independently halogen, is NH 2 , NH(CI-C 6 alkyl), N(CI-C 6 alkyl) (C -C 6 alkyl) or methyl. Embodiment A138. Compounds according to embodiment A137, wherein Xb or Xc is -NI% 6 R NR 6 RT-(Cz-C alkyl)-, -C(O)NR 6 RT, -S0 2 NR Rv, or halogen; wherein R 6 and R are independently at each occurrence H, Cz-C alkyl, Cz-C 6 alkoxy, Cz-C alkoxy CI-C 6 alkyl, Cz-C 6 alkoxycarbonyl, OH, Cz-C 6 hydroxyalkyl, -(C 1 -C 4 )alkyl- CO 2 - alkyl, pyridyl Cz-C alkyl, Cz-CG al kanoyl, benzyl, phenyl CI-C 6 alkoxy, or phenyl Cz-C 6 alkanoyl, wherein each of the above is unsubstituted or substituted with !, 2, or 3 groups that are independently, halogen, C -C 6 cycloalky!, C -C alkoxy, piperidiny! C 1 -C aikyl, morpholinyl CI-C alkyl, piperazinyl C -C a!kyl, OH, SH, NH 2 N H(alkyl), N(a!kyl) alkyl), -O-C -C 4 alkanoyl, C 1 -C alkyl, CF 3 , or OCF ; or R{, R and the nitrogen to which they are attached form a morpholiny!, [hiomorpholinyl, piperidinyl, pyrrol idinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups [hat are independently C -C 4 aikyl, C - C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment A139. Compounds according to embodiment wherein R=, and the nitrogen to which they are attached form a morpholiny!, thiomoroholinyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, C -C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment AI40. Compounds according to embodiment wherein R and the nitrogen to which they are attached form a piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment AI41. Compounds according to embodiment wherein and R? are independently at each occurrence H, C -C 6 alkyl, CI-CG alkoxy, CI-C 6 alkoxy CI-C alkyl, C -C 6 alkoxycarbonyl, OH, CI-C 6 hydroxyalkyl, -(CI-C 4 }alkyl-CO 2 - alkyl, pyridyl CI-C 6 alkyl, CI-C 6 alkanoyl, benzyl, phenyl C 1-C 6 a!koxy, or pheny! C 1 -C a!kanoyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, C -C 6 cycloalkyl, C -C 6 alkoxy, piperidinyl CI-C alky!, morpho!inyl CI-C 6 alky!, mimeraziny! C:-C alkyl, OH, N'H 2 , N-H (alkyl) , N(alkyl) alkyl), -O-C:-C 4 alkanoyl, CI-C 4 alky!, CF 3 , or OCF 3. Embodiment A142. Compounds according to embodiment wherein and R 7 are independently at each occurrence H, CI-C 6 alkyl, CI-C 6 hydroxyalkyl, CI-C 6 alkoxy, CI-C 6 alkoxy Ci-C 6 alkyl, or CI-C alkanoyl, wherein each of the above is optionally substituted with i, 2, or 3 groups that are independently OH, SH, halogen, or C 3 -C cycloa!kyl. Embodiment A143. Compounds according to embodiment wherein and Xe are independently fluoro, chloro, or methyl; and hydrogen or halogen. Embodiment A144. Compounds according to embodiment wherein halogen; NH 2 , NH(CI-C 6 alkyl) or N(C -C 6 alkyl) (CI-C alkyl); and Xd are both hydrogen. Embodiment A145. Compounds according to embodiment wherein -NR 6 RT, NR 6 R 7 CI-CG alkyl, -SO 2 NR 6 R or halogen; wherein R and R are independently at each occurrence H, CI-C alkyl, CI-C 6 alkoxy, CI-C 6 alkoxy CI-C 6 alkyl, CI-C 6 alkoxycarbony!, OH, CI-C 6 hydroxyalkyl, - (Ci-C 4 )alkylCO 2-a!ky!, pyridy! Ci-C 6 alkyl, C!-CG alkanoy!, benzyl, phenyl C:-C 6 alkoxy, or phenyl CI-C alkanoy!, wherein each of the above Is unsubstitu ed or substituted with !, 2, or 3 groups that are independently, halogen, C 3 -C 6 cycloalkyl, CI-C 6 alkoxy, piperidinyl CI-C 6 alkyl, morpho!invi CI-C 6 alkyl, piperazinyl C 1 -C alkyl, OH, SH, NH 2 , NH(alkyl), N(alkyl) (alkyl), -O-CI-C 4 alkanoyl, CI-C 4 alkyl, CF 3 , or OCF 3 ; or Re, RT, and the nitrogen to which they are attached form a morphol inyl, t hiomorpho! iny!, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently C -C 4 alkyl, Ci-C 4 alkoxy, hydroxy, hydroxy C 1 -C alkyl, or halogen. Embodiment A146. Compounds according to embodiment A145, wherein Xc is fluoro, chloro, NH 2 , NH(C 1 -C 6 alkyl), N(CI-C alkyl) (CI-C 6 alkyl), -SO 2 N-H 2 , -SO 2 NH(CI-C alkyl), -SO 2 N(CI-C 6 alkyl) (CIC 6 alkyl), or piperazinyl, wherein the piperazinyl group is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment A147. Compounds according to either embodiment A137 or A144, wherein Xc is -C(O)NR 6 Rv, -(CI-C 6 alkyI)-C(O)N-R Rv, NR 6 Rv, or NR RT-(CI-C 6 alkyl)-; wherein R 6 and R are independently at each occurrence H, CI-C 6 alkyl, CI-C alkoxy, CI-C 6 alkoxy CI-CG alkyl, CI-C 6 alkoxycarbonyl, OH, CI-C 6 hydroxya!kyl, - (CI-C 4 )alkylC0 2-alkyl, pyridyl C -C alkyl, C -C 6 alkanoyl, benzyl, phenyl C 1 -C alkoxy, or phenyl CI-CG a!kanoyl, wherein each of the above is unsubstituted or or 3 groups that are substituted with I, 2, C -C cyc!oalkyl, C 1 -C independently, halogen, al ky!, morphol invl C - C 6 alkoxy, piperidinyl C!-C 6 alkyl, piperazinyl CI-C 6 alkyl, OH, NH 2 , bq4(alkyl) , N(a!kyl) (alkyl), -O-CI-C 4 alkanoyl, CI-C 4 alkyl, CF 3 , or OCF 3 ; or Re, RT, and the nitrogen to which they are attached form a morpholinyl, thiomorpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, Ci-C 4 alkoxy, hydroxy, hydroxy C -C 4 alkyl, or halogen. Embodiment A148. Compounds according to embodiment wherein hydrogen; and C!-C 6 alkyl or CI-C 6 alkanoyl, each of which is optionally substituted with I, 2, or 3 groups that are independently NH 2, NH(C 1 -C 6 alkyl), N(CI-CG alkyl) (CI-C alkyl), OH, SH, cyclopropyl, or Ci-C 4 alkoxy. Embodiment A148a. Compounds according to embodiment wherein is CI-CG alkanoyl optionally substituted with I, 2, or 3 groups that are independently OH, cyclopropyl, or NH 2 . Embodiment A149. Compounds according to embodiment wherein hydrogen; me, or Xd is -C(O)NR 6 Rv, -(C 1 -C 6 alkyI)-C(O)NR 6 RT, NR 6 RT, NR 6 R -(CI-C 6 alkyl)- or -C0 2 -(CI-C )alkyI; wherein R 6 and Rv are independently at each occurrence H, CI-C alkyl, C:-C 6 alkoxy, CI-C 6 alkoxy C -C alkyl, C!-C alkoxycarbonyl, OH, C!-C 6 hydroxya!kyl, - (CI-C 4 )a!kyiCO 2-alkyl, pyridyl CI-C alkyl, C -C 6 alkanoy!, benzyl, phenyl C._-C 6 alkoxy, or phenyl C:-C 6 alkanoyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, C -C 6 cycloalkyl, CI-C 6 alkoxy, piperidinyl CI-C 6 alkyl, morphoiinyl C!-C 6 alkyl, piperazinyl CI-CG alky!, OH, NH 2 , NH(alkyl) , N(alkyl) (alkyl), -o-e 1 -c 4 aikanoyl, CI-C 4 alkyl, CF or OCFa; or Re, R and the nitrogen to which they are attached form a morpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, CI-C 4 aikoxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen; and hydrogen, methyl, CI-C 2 alkoxy, or halogen. Embodiment AI50. Compounds according to embodiment wherein is NR RT, or Nroff-(CI-C6 6 alkyl)-, -C(O)NR 6 Rv or -CO 2 -(C 1 - CG)alkyl; wherein hydrogen or CI-C 4 alkyl; OH, CI-C 6 alkyl or CI-C 6 alkanoyl, wherein the alkyl and alkanoyl groups substituted with I, 2, or 3 groups that are independently NH 2 , NH(CI-CG alkyl), N(CI-C 6 alkyl) (CI-C 6 alkyl), C 3 -C 6 cycloalkyl, OH, or CI-C 4 alkoxy. Embodiment AI51. Compounds according to embodiment wherein halogen; is NR 6 RT, NR 6 R -(C 1 -C 6 alky!)-, -C(O)NR RT, halogen, -C0 2 -(C 1 - C )a!kyl, NH 2 , .h[H.(C 1 -C alkyl), N(C 1 -C alky!)(Ci-C a!kyl), -S0 2 NH 2, -S0 2 NH (C 1 -C alkyl) , -S0 2 N (C -C 6 alkyl) (C 1 -C alkyl), or pipera=inyl, wherein the piperazinyl group is optionally substituted with ! or 2 groups that are independently CI-C 4 alkyl, C 1 -C alkoxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen; is hydrogen; is H, methyl, hTH 2 , k[H(CI-C alkyl) or N(C 1 -C 6 alkyl) (Ci-C 6 alkyl) . Embodiment A152. Compounds according to embodiment A!35, wherein X 2 , Xa, Xb, Xc, Xd, and Xe are independently selected from H, OH, halogen, CF 3 , alkyl, OCF 3 , pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, thienyl, furyl, pyrrolyl, piperidinyl, piperazinyi, or C 3 -C cycloalkyl, wherein each of the above is optionally substituted with -NR 6 R -C(O)NR R NR R -(CI-C 6 alkyl)-, CI-C alkyl, CI-C alkoxy, or halogen. Embodiment A153. Compounds according to embodiment A152, wherein at least three of X 1 , X 2 , Xa, Xb, Xc, Xa, and X. hydrogen. Embodiment A154. A compound of the formula: R 2 R3 RI R 4" "N "0 I R pharmaceutically acceptable salt thereof, wherein alkanoyl, ha!ogen, arylalkanoyl, ary!alkyl, alkoxyalkyl, hydroxya!kyl, or carboxa!dehyde, wherein the aryl portion of arylaikyl, and ary!alkanoy! is unsubstituted or substituted with i, 2, 3, 4, or groups that are independently ha!ogen, C=-C alkyl, CI-C 4 aikoxy, nitro, CN, ha!oalkyl, haloalkoxy or CO 2 H; the alkyl portion of the hydroxya!ky!, arylalkyl, alkanoyl, a!koxyalkyl and ary!alkanoyl groups are unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, methoxy, ethoxy or spirocyclopropyl; arylalkoxy, aryloxy, phenyloxy(C 1 -C 6 )alkyl, OH, halogen, arylthioalkoxy, alkoxy, -OC (O) k (CHa) naryl, -OC (O) N (alkyl) (CH 2 ) nary!, alky!, alkoxyalkoxy, dialkylamino, pyridyl, pyrimidyl, pyridasyl, pyrazolyl, imidazolyl, pyrrolyl, [etrahydroquinolinyl, tetrahydroisoquinolinyl, tetrazolyl, pyrazinyl, benzimidazolyl, triazinyl, tetrahydrofuryl, piperidinyl, hexahydropyrimidinyl, thiazolyl, thienyl, or CO 2 H, wherein n is 0, i, 2, 3, 4, 5 or 6; the aryl portion of arylalkoxy, aryloxy, arylthioalkoxy, -OC(O)NH(CH 2)naryI, and -OC(O)N(alkyl) (CH 2 )naryl or the heteroaryl and heterocycloalkyl groups is unsubstituted or substituted with I, 2, 3, 4, or groups that are independently halogen, -(CI-C )alkyIN(R)-CO 2 R 0, haloalkyl, heteroaryl, heteroarylalkyl, NR RT, Nroff-(CI-CG alkyl)-, -OC(O)NR 6 RT, wherein R and R are independently at each occurrence H, alkyl, alkoxy, alkanoyl, arylalkyl, arylalkoxy, or arylalkanoyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, OH, SH, C 3-C 6 cycioalky!, alkoxy, a!kyl, haloalkyl, or haloalkoxy; or R 6, R and the nitrogen to which they are attached form a morpholiny!, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,Sdioxide, piperidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, alkoxycarbonyl, hydroxyl, hydroxya!kyl, or halogen; R at each occurrence is independently H or CI-C 6 alkyl; R 30 is C 1 -C 6 alkyl optionally substituted with 1 or 2 groups that are independently OH, SH, halogen, amino, monoa!kylamino, dia!kylamino or C -C 6 cycloalkyl; halogen, aryla!koxycarbonyl, aryloxycarbonyl, arylalkyl, -OC(O)NH(CH 2)nary1, arylalkoxy,---OC(O)N(alkyl) (CH 2 )naryl, aryloxy, arylthio, thioalkoxy, arylthioalkoxy, alkenyl, NR 6 Rv, NR 6 R -(CI-C alkyl)-, or alkyl, wherein the aryl portion of arylalkoxycarbonyl, aryloxycarbonyl, arylalkyl, -OC(O)NH(CH 2 )naryI, arylalkoxy, -OC(O)N(alkyl) (CH 2 )naryl, and arylthioalkoxy, is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, alkoxy, alkyl, haloalkyl, or haloalkoxy, wherein n is 0, i, 2, 3, 4, 5, or 6; or H, alkyl substituted with one group selected from CO,H, - CO 2-(Ci-C 6)alkyl, -C(O)NRR, -N(R 30 )C(O)NRR, -N(R 30 )C(O)-(CI- C )alkoxy, and -NR Rv, arylalkoxy, arylalkyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, or alkoxyalkoxy, wherein the aryl portion of arylalkoxy, arylalky! is unsubstituted or substituted with !, 2, 3, 4, or groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, haioa!kyl, or ha!oalkoxy; and is alalky!, alky!, ary!, a!koxy, heterocycloa!kyialky!, heteroarylalky!, ary!thioalkyl, heterocycloaiky!, or heteroaryl, wherein each of the above is unsubs ituted or substituted with I, 2, 3, 4, or 5 groups that are independently a!kyl, halogen, a!koxy, arylalkoxy, thioalkoxy, alkoxycarbonyl, arylalkoxycarbonyl, C0 2 H, CN, amidinooxime, NR 6 Rv, NR RT-(CI-C 6 alkyl-, -C(O)NR 6 R amidino, haloalkyl, or haloalkoxy. Embodiment AI60. Compounds according to embodiment wherein is halogen,(C 1-C 6)alkanoyl, phenyl(C 1 -C 6 )alkanoyl, naphthyl(C 1-C 6)alkanoyl, naphthyl(C 1 -C )alkyl, phenyl(C 1 - C )alkyl, alkoxyalkyl, hydroxyalkyl, or carboxaldehyde, wherein the phenyl and naphthyl portions of the above are unsubstituted or substituted with i, 2, 3, 4, or groups that are independently halogen, CI-C 4 alkyl, Cz-C 4 alkoxy, nitro, CN, CF 3 , OCF 3 or C0 2 H; the alkyl portion of the above groups are unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, methoxy, or ethoxy. is phenylalkoxy, aryloxy, phenyloxy(Ci-C )alkyl, OH, halogen, phenylthioalkoxy, alkoxy, alkyl, alkoxyalkoxy, -OC(O)NH(CH 2)nphenyl, -OC(O)N(alkyl) (CH 2 )nphenyl, pyridyl, pyrimidyl, pyridazyl, pyrazolyl, or thienyl, wherein the above groups are unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently halogen, - (C -C ) a!kyl-N (R) -CO,R 30 , halo (C -C 4 ) a!kyl, or thienyl ; R 3 is halogen, phenylalkoxycarbonyl, phenyloxycarbony!, phenyl (C -C ) alkyl, phenylalkoxy, phenyloxy, phenylthio, thioalkoxy, arylthioalkoxy, (C 2 -C 6 ) alkenyl, NR R NR 6 R - (CI-C alkyl-, or alkyl, wherein the phenyl, naphthy!, and aryl portions of arylalkoxycarbonyl, aryloxycarbony!, arylalkyl, -OC (O) NH (CH 2 ) naryl, arylthioalkoxy, arylalkoxy, and-OC (O) N alkyl) (CH 2 ) nary!, are unsubstituted or substituted with 1, 2, or 3 groups that are independently, halogen, alkoxy, alky!, CF 3 , or OCF 3 , wherein n is 0, I, 2, 3, 4, 5, or 6; or R is H, (CI-C 6 ) alkyl substituted with one group that is CO 2 H, -CO 2-(Ci-C 6)alkyl, -C(O) NRR, -N(R 30 )C(O)NRR, -N(R 30 )C(O)- (Ci-C 6)alkoxy, or -NR 6 RT, phenylalkoxy, phenyl(Ci-C 6 )alkyl, hydroxyalkyl, haloalkyl, alkoxyalkyl, or alkoxyalkoxy, wherein the phenyl portion of the above groups are unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, CF 3 , or OCF 3 . Rs is phenyl (CI-C ) alkyl, (CI-C 6 ) alkyl, phenyl, naphthyl, pyridyl, (CI - C 6 ) alkoxy, piperidiny1 (CI-C 6 ) alkyl, pyrrolyl (CI-C 6 ) alkyl, imidazol idinyl (CI-C 6 ) alkyl, pyrazolyl (CI-C 6 ) alkyl, imidazolyl (CI-C 6 ) alkyl, tetrahydropyridinyl (CI-C 6 ) alkyl, thienyl (CI-C ) alkyl, phenylthio (CI-CG) alkyl, or pyridyl (CI-CG) alkyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently (CIC 4 ) alkyl, fluoro, chloro, bromo, (C 1 -C 4 ]alkoxy, pheny! (C:-C )alkoxy, hio(C:-C 4 alkoxy, {Ci-C 4 alkoxycarbony!, phenyl(C 1 - C 4)alkoxycarbonyl, CO 2 H, CN, amidinooxlme, NR 6 R NR 6 R -(C - C alkyl)-, -C(O)NR 6 R amldino, CF 3 , -C? 2 CF OCF or OCF 2 CF 3. Embodiment AI6!. Compounds according to embodiment A!60 wherein R: is halogen, (C 1 -C )alkanoyl, phenyl(C 1 -C )alkanoyl, benzyl, phenethyl, phenpropyl, hydroxyalkyl, or carboxaldehyde, wherein the above phenyl groups are unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, CI-C 4 alkyl, C:-C 4 alkoxy, nitro, CN, CF 3 , OCF 3 or CO 2 H; the alkyl portion of the above groups are unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, methoxy, or ethoxy; R 2 is benzyloxy, phenethyloxy, phenpropyloxy, phenbutyloxy, phenyloxy, phenyloxy(CI-C 6 )alkyl, OH, halogen, phenylthioalkoxy, alkoxy, alkyl, alkoxyalkoxy, wherein n is 0, i, 2, 3, or 4, and the above groups are unsubstituted or substituted with i, 2, or 3, groups that are independently halogen, -(CI- C 6 )alkyI-N(R)-CO 2 R 0 , halo(Ci-C 4 )alkyl, or thienyl; R is halogen, phenylalkoxycarbonyl, phenyloxycarbonyl, phenyl(Ci-C 6)alkyl, phenylalkoxy, phenyloxy, phenylthio, thioalkoxy, phenylthioalkoxy, (C 2 -C 6 )alkenyl, NR R NR 6 Rv CI-C 6 alkyl, or alkyl, wherein the above phenyl groups are unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, alkoxy, (Ci-C 4 )alkyl, CF 3 , or OCF 3 , H, (CI-C 6 ) alky! substituted with one group that is CO 2 H, -CO -(C:-C 6)alkyl, -C(O)NRR, -N(R 3 )C(O)NRR, -N(R 30 )C(O)- (C 1-C )alkoxy, or -NR R pheny!a!koxy, benzy!, phenethyl, hydroxyalky!, haioalkyl, alkoxyaikyl, or a!koxya!koxy, wherein the phenyl portion of the above groups are unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, hydroxy, (C 1 -C 4 )alkoxy, (C 1 - C 4)alkyl, nitro, CF 3 , or OCF 3 . is benzyl, phenethyl, phenpropyl, phenbutyl, (C 1 -C 6 )alkyl, phenyl, or pyridyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently (C -C 4 ) alkyl, f luoro, chloro, bromo, (C 1-C 4)alkoxy, phenyl(C 1 -C 4 )alkoxy, thi 0 (C 1 -C 4 )alkoxy, (C 1 - C 4)alkoxycarbonyl, CO 2 H, CN, amidinooxime, NR 6 RT, NR 6 R - (C!- C 6 alkyl)-, -C (O) NR 6 R amidino, CF 3 , or OCF 3 . Embodiment A!62. Compounds according to embodiment AI61 wherein is bromo, phenyl(C 1 -C 4 )alkanoyl, benzyl, phenethyl, phenpropyl, hydroxyalkyl, or carboxaldehyde, wherein the above phenyl groups are unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, CI-C 4 alkyl, CI-C 4 alkoxy, nitro, CN, CF 3 , OCF 3 or CO 2 H; is benzyloxy, phenethyloxy, phenpropyloxy, phenbutyloxy, phenyloxy, phenyloxy(C -C 6 )alkyl, OH, halogen, or phenylthioalkoxy, wherein n is 0, I, 2, 3, or 4, and the above groups are unsubstituted or substituted with i, 2, or 3, groups that are independently halogen, -(CIC 6)alkyl-N(R)-CO 2 R 0, hal 0 (C 1 -C 4 )alkyl, or thienyl; is bromo, phenyl a! koxycarbonyl, phenyloxycarbonyl, phenyl (Ci-C 6 ) a!kyl, phenylalkoxy, phenyloxy, pheny!thio, thioalkoxy, pheny!thioalkoxy, (C 2 -C 6 )alkenyl, NR R NR R 7 C!-C alkyl, or alkyl, wherein the above phenyl groups are unsubstituted or substituted with 1, 2, or 3 groups that are independent i y, halogen, alkoxy, (C 1 -C 4 )a!kyl, CF or OCF 3 , H, (CI-C ) alkyl substituted with one group that is CO 2 H, -CO 2- (CI-C 6 ) alky!, -C (O)NRR, -N (R] 0 ) C (O) NRR, -N (R 30 ) C (O) - (Ci-C 6) a!koxy, or -NR R 7 , phenylalkoxy, benzyl, or phenethyl, wherein the phenyl portion of the above groups are unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, hydroxy, (C -C 4 )alkoxy, (C 1 - C 4)alkyl, nitro, CF 3 , or OCF 3 . is benzyl, phenethyl, phenpropyl, (C 1 -CG)alkyl, phenyl, or pyridyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently (C 1-C 4)alkyl, fluoro, chloro, bromo, (C 1 -C 4 )alkoxy, CO 2 H, CN, amidinooxime, amidino, CF 3 , OCF 3 , NR 6 R NR 6 RT- (CI-C 6 alkyl)-, 0 r-C(O)NR 6 Rv; wherein R 6 and R are independently hydrogen, OH, CI-C 4 alkoxy, CICG alkanoyl, or CI-CG alkyl, wherein each of the above is optionally substituted with 1 or 2 groups that are independently OH, N-H 2 , C 3 -C cycloalkyl, or halogen; or R 6, Rv, and the nitrogen to which they are attached form a morphol inyl, piperidinyl, pyrrol idinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen. Embodiment A163. Compounds of the formula R 2 R3" RI R 4 AN I Rs pharmaceutically acceptable salts thereof, wherein is H, halogen, alkyl, carboxaldehyde, hydroxyalky!, arylalkoxy, arylalkyl, CN, alkanoyl, alkoxy, aikoxyalky!, or arylalkanoyl, wherein the aryl portion of arylalkoxy, arylalkyl, and arylalkanoyl is unsubstituted or substituted with I, 2, 3, 4, or 5 groups that are independently halogen, Ci-C 4 alkyl, CI-C 4 alkoxy, nitro, CN, haloalkyl, haloalkoxy or CO 2 H; wherein the alky! portion of the alkyl, hydroxyalkyl, aryla!koxy, ary!alkyl, alkanoyl, alkoxy, alkoxyalkyl and aryialkanoyl groups is unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, methoxy, ethoxy or spirocyclopropyl; is H, arylthio, -OC(O)NH(CH 2 )naryI, arylalkyl, -OC(O)N(alkyl) (CH 2 )naryl, or arylthioalkoxy, wherein n is I, 2, 3, 4, or 5; wherein the aryl groups are optionally substituted with I, 2, 3, 4, or 5 groups that are independently halogen, -(CI-C 6 )alkyI-N(R)-CO 2 R 0 , CI-C 4 alkoxy, CI-C 4 alkyl, CF 3 , or OCF ; R at each occurrence is independently H or CI-C alkyl; R 30 is CI-C alkyl optionally substituted with 1 or 2 groups that are independently OH, SH, halogen, amino, monoalkylamino, dialkylamino or C 3 -C 6 cycloalkyl; is halogen, alkoxycarbonyl, arylalkoxycarbonyl, aryloxycarbonyl, arylalkyl, -OC(O)NH(CH 2 )naryl, arylalkoxy, -OC(O)N(alkyl) (CH 2 ) aryl, aryloxy 1 arylthio, thioalkoxy, arylthioalkoxy, alkeny!, NR 6 R 7 C:-C alkyl, NR 6 R 7 or alkyl, wherein the aryl portion of arylalkoxycarbony!, ary!oxycarbonyi, arylalkyl, -OC(O)NH(CH 2 )=ary!, arylalkoxy, -OC(O)N(alkyl) (CH 2 )naryl, and arylthioalkoxy, is unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, alkoxy, alkyl, haloalkyl, or ha!oalkoxy, wherein n is 0, I, 2, 3, 4, 5, or 6; or H, alkyl substituted with one group that is CO,H, -CO=- (Ci-C 6)alkyl, -C(O)NRR, -N(R 30 )C(O)NRR, -N(R 30 )C(O)-(C 1 - C 6)alkoxy, or -NR 6 RT, arylalkoxy, arylalkyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, or alkoxyalkoxy, wherein the aryl portion of arylalkoxy, arylalkyl is unsubstituted or substituted with I, 2, 3, 4, or groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, haloalkyl, or haloalkoxy; and is arylalkyl, alkyl, aryl, alkoxy, heterocycloalkylalkyl, heteroarylalkyl, arylthioalkyl, heterocycloalkyl, or heteroaryl, wherein each of the above is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently alkyl, halogen, alkoxy, arylalkoxy, thioalkoxy, alkoxycarbonyl, arylalkoxycarbonyl, CO 2 H, CN, amidinooxime, krR 6 R NR R -(CI-C alkyl)-, -C(O)NRGR amidino, haloalkyl, or haloalkoxy; wherein R 6 and Rv are independently at each occurrence H, C -C alkyl, Cz-C alkoxy, CI-C 6 alkoxy CI-C alkyl, CI-C 6 alkoxycarbonyl, OH, CI-C 6 hydroxyalkyl, -(C 1 -C 4 )alkyl- C0 2 -alkyl, pyridyl CI-C 6 alkyl, CI-C 6 alkanoyl, benzyl, phenyl CI-C alkoxy, or phenyl CI-C 6 alkanoyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, C -C 6 cycloal kyl, Ci -C alkoxy, piperidiny! CI-C a!kyl, morpho!inyl CI-C alkyl, pipera inyl C:-C alkyl, OH, SH, kq£ 2 b-H(alkyl), N(alkyl) (alky!), -0-C -C 4 alkanoy!, CI-C a!ky!, CF 3 , or OCF 3 ; or R 6, RT, and the nitrogen to which they are attached form a morphol inyl, thiomorphol inyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently CI-C 4 a!kyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 a!kyl, or halogen. Embodiment A168. Compounds according to embodiment A163 wherein R s is benzyl, phenethyl, phenpropyl, phenbutyl, alkyl, phenyl, alkoxy, pyridyl (CI-C ) alkyl, phenyl (CI-C ) thioalkyl, pyrrolyl, pyrrolyl(Ci-C 6 )alkyl, or pyridyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently (C -C )alkyl, halogen, (C -C 6) alkoxy, phenyl (CI-C ) alkoxy, (CI-C ) thioalkoxy, alkoxycarbonyl, CO 2 H, CN, amidinooxime, amidino, CF 3 , or OCF 3. Embodiment A169. Compounds according to embodiment A163 wherein R 1 is H, CI, Br, (Ci-C )alkyl, carboxaldehyde, hydroxy(C 1 - C )alkyl, wherein the alkyl portion of above is unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, methoxy, or ethoxy is H, phenyl hio, -OC (0) !T£ (CH ) naryl, pheny!aiky!, -OC (0) N (a!kyl) (CH=) acrylic, or phenyl :hlo (C--C ) a!koxy, wherein n is !, 2, 3, or 4; wherein the ary! groups are opnionaiiy subs-'_tu=ed wi=h i, 2, 3, 4, or 5 groups that are niependen=!y halogen, - (C -C 6 )alkyl-N[R)-CO..R 30 , CI-C 4 a!koxv, C:-C aikyi, CF 3 , or OCF 3 ; is bromo, alkoxycarbonyl, pheny! a! koxycarbonyl, pheny!oxycarbonyl, phenylalkyl, phenylalkoxy, phenyloxy, phenylthio, thioalkoxy, phenyl thioalkoxy, a!kenv!, N<R 6 R or alkyl, wherein the phenyl portion of the above is unsubstituted or substituted with !, 2, or 3 groups that are independently, halogen, (C:-C 4 ) alkoxy, (CI-C 4 ) alkyl, halo(C 1-C 4)a!kyl, or halo(Ci-C 4 )a!koxy, wherein n is 0, i, 2, 3, or 4; H, alkyl substituted with one group that is C0 2 H, -CO 2 - (C 1-C )alkyl, -C(O)NRR, -N(R 30 )C(O)NRR, -N(R 0 )C(O)- (C 1 - C 6) alkoxy, or -NR 6 RT, phenylalkoxy, phenylalkyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, or wherein the phenyl portion of phenylalkoxy, phenylalkyl is unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, haloalkyl, or haloalkoxy benzyl, phenethyl, phenpropyl, phenbutyl, alkyl, phenyl, phenyl(CI-C 6)thioalkyl, pyrrolyl, or pyridyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently (Ci-C )alkyl, halogen, (CI-C 6) alkoxy, benzyloxy, (CI-C 6 ) thioalkoxy, alkoxycarbonyl, CO 2 H, CN, amidinooxime, amidino, CF 3 , or OCF 3 ; R 6 and R are independently hydrogen, OH, CI-C 4 alkoxy, CIC alkanoyl, or CI-C alkyl, wherein each of the above is optionally substituted with i cr 2 groups that are independently OH, 2 , C 3 -C cycloa;ky!, or halogen; or R 6, Rv, and the nitrogen to which they are attached form a morpho!inyl, piperidinyl, pyrrol idlnvl, or piperaziny! ring which is optionally subs ±tued wiZh 1 or 2 groups that are independently C -C alkyl, C -C 4 a!koxy, hydroxy, hydroxy C:-C 4 alkyl, or halogen. Embodiment AI70. Compounds according to embodiment 1 R 3 RI R 4 "N -O Rs pharmaceutically acceptable salt thereof, wherein is H, halogen, alkyl, carboxaldehyde, hydroxyalkyl, arylalkoxy, arylalkyl, CN, alkanoyl, alkoxy, a!koxyalkyl, or arylalkanoyl, wherein the a yl portion of arylalkoxy, arylalkyl, and arylalkanoyl is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently halogen, CI-C 4 alkyl, CI-C 4 alkoxy, nitro, CN, haloalkyl, haloalkoxy or CO=H; wherein the alkyl portion of the alkyl, hydroxyalkyl, arylalkoxy, arylalkyl, alkanoyl, alkoxy, alkoxyalkyl and arylalkanoyl groups is unsubstituted or substituted with I, 2, or 3 groups that are independently halogen, methoxy 0 ethoxy or spirocyc!opropyl; is arylalkoxy, aryloxy, aryloxyalkyl, OH, halogen, arylthioalkoxy, alkoxy, -OC(O)NH(CH 2 )naryI, -OC (0) N (a!kyl) (CH 2 ) r.ary!, a!kyl, alkoxyaikoxy, dia!ky!amino, or CO,H, wherein n is 0, i, 2, 3, 4, 5 or 6; the aryl port'_on of arylalkoxy, ary!cxy, ary--h oa!kexv, -OC (O) NH (CH 2 ) r aryl, and -OC (O) N (a!ky!) (CH: -.aryl or he heteroaryi and heterocycloal ky! groups is unsubst!tuted or substituted with i, 2, 3, 4, or groups that are independent!y halogen, -(C:-C )alky!- N (R) -C0 2 R 30 , haloalkyl, he-eroaryi, heteroary!alkyl, NR R k R R -(C 1 -C aikyl)-, -OC(O)NR R wherein R 6 and R are independently at each occurrence H, CI-C alkyl, CI-C 6 alkoxy, CI-C 6 alkoxy CI-C 6 alkyl, CI-C 6 alkoxycarbonyl, OH, CI-C 6 hydroxyalkyl, - (C 1 -C 4 )alkylCO 2-alkyl, pyridyl CI-C 6 alkyl, C 1 -C a!kanoyl, benzyl, phenyl C 1 -C alkoxy, or phenyl CI-C alkanoyl, wherein each of the above is unsubstituted or substituted with 1, 2, or 3 groups that are independently, halogen, C 3 -C 6 cyc!oalkyl, Ci-C 6 alkoxy, plperidinyl CI-C alkyl, morpholinyl CI-C alkyl, piperazinyl C -CG alkyl, OH, SH, NH 2 , NH(alkyl), N(alkyl) (alkyl), -O-CI-C 4 alkanoyl, CI-C 4 alkyl, CF 3 , or OCF 3 ; or R 6, R and the nitrogen to which they are attached form a morphol i nyl, t hiomorphol inyl, piperidinyl, pyrrolidinyl, or piperazinyl ring which is optionally substituted with 1 or 2 groups that are independently C -C 4 alkyl, CI-C 4 alkoxy, hydroxy, hydroxy CI-C 4 alkyl, or halogen; R at each occurrence is independently H or CI-C 6 alkyl; R 30 is C -C alkyl optionally substituted with 1 or 2 groups that are independently OH, SH, halogen, amino, monoalkylamino, dialkylamino or C 3 -C 6 cycloalkyl ; is halogen, alkoxycarbcny!, arylalkoxycarbonyl ary!oxycarbonyl, arylalkyl, -OC (O)NH (CH 2 ) naryl arylalkoxy, -OC(OI N Calky!l (CH ) Daryl, aryloxy, aryl hic thioa!koxy, arylthioalkoxy, a!kenyl, NR 6 R C -C 6 alky! NR R or alkyl, wherein the aryl portion of arylalkoxycarbonyl, ary!oxl;carbonyl arylalkyl, -OC (0) (CH 2 ) naryl, arv!alkoxv -OC (0)N (a!kyl)(CH 2 ) naryl, and arylthioalkoxy, is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, alkoxy, alkyl, haloalkyl, or haloalkoxy, wherein n is 0, I, 2, 3, 4, 5, or 6; or is H, alkyl substituted with one group that is C0 2 H, -CO.- (C -C 6)alkyl, -C(O)NRR, -N(R 30 )C(O)NRR, -N(R 30 )C(O)- (C 1 - C )alkoxy, or -NR R aryla!koxy, arylalkyl, hydroxyalkyl, ha!oalkyl, a!koxy, alkoxyalkyl, or alkoxyalkoxy, wherein the aryl portion of aryla!koxy, arylalkyl is unsubstituted or substituted with I, 2, 3, 4, or groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, haloalkyl, or haloalkoxy; and is aryl, heterocycloalkyl alkyl, heteroarylalkyl, arylthioalkyl, heterocycloalkyl, or heteroaryl, wherein each of the above is unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently alkyl, halogen, alkoxy, arylalkoxy, thioalkoxy, alkoxycarbonyl, arylalkoxycarbonyl, CO 2 H, CN, (CI-C alkyl) -, -C (0) NI% R haloalkoxy. amidinooxime, NR 6 RT, NRGRv- amidino, haloalkyl, or Embodiment A173. Compounds according to embodiment wherein is H, halogen, alkyl, carboxa!dehyde, hydrox.va ikyl, benzyloxy, Dhenet hvloxv mhenDropv! oxv, ' .... phenethy!, phenpropy!, CN, a!kanoyl, aikoxv, cr phenylC(O)-, phenylCH 2 C(O)-, or pnenv_uH;CH.u(O) wherein the above phenyi groups are unsubstl cured or substituted with I, 2, or 3 groups thaare independently halogen, C -C aikyl, C!-C aikcxy, nitro, CN, CF 3 , OCF or C0 2 H; wherein the above alky! groups are unsubstituted or substituted with !, 2, or 3 groups that are independently halogen, methoxy, or ethoxy; is benzyloxy, phenet hyloxy, phenpropyloxy, pheny!oxy, phenyloxy (C -C 6 ) alkyl, OH, halogen, phenyl thioalkoxy, alkyl, alkoxy, -OC (O)NH (CH ) nphenyl, - OC(O)N(alkyl) (CH 2 ) phenyl, dialkylamino, or CO 2 H, wherein n is 0, I, 2, 3, or 4; the above aryl groups are unsubstituted or substituted with i, 2, 3, 4, or 5 groups that are independently halogen, - (C!-C 6 ) alkyl-N (R) -CO 2 R 30 , CF 3 , pyridyl, thienyl, NR R or NR 6 R -(C!-C 6 alkyl)-, wherein R 6 and R are independently at each occurrence H, alkyl, alkanoyl, benzyl, or phenylC (0) -, wherein the phenyl portion of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently, halogen, OH, C 3 - C 6 cycloalkyl, alkoxy, alkyl, CF or OCF 3 ; is halogen, alkoxycarbonyl, phenyl al koxycarbonyl, phenyloxycarbonyl, phenylalkyl, -OC (O) N-H (CH 2 ) nphenyl, phenylalkoxy, -OC (O) N (alkyl) (CH 2 ) phenyl, phenyloxy, phenylthio, thioalkoxy, phenyl thioalkoxy, alkenyl, NR 6 Rv or alkyl, wherein the pheny! portion of the above is unsubst i cured or substituted with I, 2, or 3 groups that are independently, halogen, alkoxy, alkyl, haloalkyl, or haloalkoxy, wherein n is 0, !, 2, 3,or 4; is H, alky! substituted with one group that is C0 2 H, -CO - (C 1-C 6)alkyl, -C(O)NRR,-N(R 30)C(O)N R, -N(R 3 )C(O)-(CIC )alkoxy, or -k 6 R pheny!alkoxy, phenyia!ky!, hydroxya!kyl, ha!oa!kyl, alkoxy, alkoxyalk}'/, or alkoxyalkoxy, wherein the pheny! portion of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, haloa!kyl, or haloalkoxy; and is phenyl, naphthyl, pyrrolylalky! 0 piperidinylalkyl pyridinylalkyl, pyrimidinylalkyl, phenylthioalkyl, pyrrolyl, piperidinyl, pyridyl, or thienylalkyl, wherein each of the above is unsubstituted or substituted with I, 2, or 3 groups that are independently alkyl, halogen, alkoxy, phenyialkoxy, thioalkoxy, alkoxycarbonyl, phenylalkoxycarbonyl, CO 2 H, CN, amidinooxime, NR 6 Rv, NR R - (CI-C alkyl-, -C(O)NR 6 R amidino, haloalkyl, or haloalkoxy. Embodiment A174. Compounds according to embodiment wherein is H, halogen, alkyl, carboxaldehyde, hydroxyalkyl, benzyloxy, phenethyloxy, benzyl, phenethyl, CN, (C - C 6)alkanoyl, alkoxy, or phenylC (O) -, or phenyiCH 2 C (0) -, wherein the above phenyl groups are unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, C 1 -C 4 alkyl, Ci-C 4 alkoxy, nitro, CN, CF 3 , OCF 3 or CO,H; is benzyloxy, phenethyloxy, phenpropyloxy, phenyloxy, phenyloxy (CI-C ) alkyl, halogen, phenyl (CI-C 4 ) thioalkoxy, dialky!amino, wherein n is 0, i, 2, 3, or 4; the above phenyl groups are unsubscituted or substi=uted with !, 2, or 3 groups that are independently halogen, CF 3 , NR 6 R or b R 7 IC: C 6 alky!) , "' = = R 6 and R are independently at each occurrence H, (C 1-C )alkyl, acetyl, benzyl, or phenvlC(O)-, wherein the phenyl portion of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently, halogen, OH, cyclopropy!, alkoxy, alkyl, CF 3 , or OCF 3 ; is halogen, alkoxycarbonyl, phenylalkoxycarbonyl, phenyloxycarbonyl, phenyla!kyl, phenylalkoxy, phenyloxy, phenylthio, thioalkoxy, phenylth calkoxy, alkenyl, NR R or alkyl, wherein the phenyl portion of the above Is unsubstituted or substituted with I, 2, or 3 groups that are independently, ha!ogen, alkoxy, alkyl, haloalkyl, or haloalkoxy, wherein n is 0, I, 2, 3,or 4; H, alkyl substituted with one group that is C0 2 H, -CO 2 - (Ci-C )alkyl, -C(O)NRR, -N(R 30 )C(O)NRR, -N(R 0 )C(O)-(C 1 - C 6)alkoxy, or -NR R phenylalkoxy, phenylalkyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, or alkoxyalkoxy, wherein the phenyl portion of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently halogen, hydroxy, alkoxy, alkyl, nitro, haloalkyl, or haloalkoxy; and phenyl, phenyl(Ci-C 4 )thioalkyl, pyridyl, or thienyl(C 1 - C 4)alkyl, wherein each of the above is unsubstituted or substituted with i, 2, or 3 groups that are independently amidinooxime, am:dino, CF 3 , or OCF Ewbodiment A175. Compounds according to embodzmen A174 wherein Rs is substituted wi:h at least one group selected from fluoro, chloro, bromo, and methyl. In another aspect, the invention provides pharmaceutical compositions comprising at least one pharmaceutically acceptable carrier, solvent, adjuvant or excipient and a compound of formula I, embodiment A66, or embodiment A154. The invention further provides pharmaceutical compositions comprising at least one pharmaceutically acceptable carrier, solvent, adjuvant or excipient and compounds according to any of the preceding embodiments. As noted above, the invention encompasses methods of treating a TNF mediated disorder, a p38 kinase mediated disorder, inflammation and/or arthritis in a subject, the method comprising treating a subject having or susceptible to such disorder or condition with a therapeutically-effective amount of a compound of formula I or embodiment AI. More specifically, the invention provides methods for treating or preventing inflammation; arthritis, rheumatoid arthritis, spondylarthropathies, gouty arthritis, osteoarthritis, systemic lupus erthematosus, juvenile arthritis, and other arthritic conditions; neuroinflammation; allergy, Th2 mediated diseases; pain, neuropathic pain; fever; pulmonary disorders, lung inflammation, adult respiratory distress syndrome, pulmonary sarcoisosis, asthma, silicosis, chronic pulmonary inflammatory disease, and chronic obstructive pulmonary disease (COPD); cardiovascular disease, arteriosclerosis, myocardial infarction (including postmyocardial infarction indications), thrombosis, congestive heart failure, cardiac reperfusion injury, as we!l as complications associated with h} ertension and/st heart failure such as vascular organ damage, res:enosis; cardiomyopathy; stroke including ischemic and hemorrhagic stroke; reperfusion injury: renal reperfusion injury; ischemia including stroke and brain ischemia, and ischemla resulting from cardiac/coronary bypass; neurotrauma and brain trauma including closed head injury; brain edema; neurodegenerazive disorders; liver disease and nephritis; gastrointestinal conditions, inflammatory bowel disease, Crohn's disease, gastritis, irritable bowel syndrome, ulcerative colitis; ulcerative diseases, gastric ulcers; ophthalmic diseases, retinitis, retinopathies, uveitis, ocular photophobia, acute injury to the eye tissue and ocular traumas such as posttraumatic glaucoma, traumatic optic neuropathy, and central retinal artery occlusion (CRAO) ; perzodontal disease; ophthalmological conditions, retinitis, retinopathies (including diabetic retinopathy), uveitis, ocular photophobia, nonglaucomatous optic nerve atrophy, and age related macular degeneration (ARMD) (including ARMD-atrophic form), corneal graft rejection, ocular neovascularization, retinal neovascularization, neovascularization following injury or infection, retrolental fibroplasias, neovascular glaucoma; glaucoma including primary open angle glaucoma (POAG), juvenile onset primary open-angle glaucoma, angle-closure glaucoma, pseudoexfoliative glaucoma, anterior ischemic optic neuropathy (AION), ocular hypertension, Reiger's syndrome, normal tension glaucoma, neovascular glaucoma, ocular inflammation and corticosteroid-induced glaucoma; diabetes; diabetic nephropathy; skin-related conditions, psoriasis, eczema, burns, dermatitis, keloid formation, scar tissue formation, angiogenic disorders; v al and bacterial infections, sepsis, septic shock, gram negative sepsis, malaria, meningitis, HIV infection, opportunistic infections, cachexia secondary to infection or malignancy, cachexia secondary to acquired immune deficiency syndrome (AIDS), AIDS, ARC (AIDS related complex), pneumonia, herpes virus; myalgias due to infection; influenza; endotoxic shock; toxic shock syndrome; autoimmune disease, graft vs. host reaction and allograft rejections; treatment of bone resorption diseases, osteoporosis; multiple sclerosis; disorders of the female reproductive system, endometriosis; hemaginomas, infantile hemagionmas, angiofibroma of the nasopharynx, avascular necrosis of bone; benign and malignant tumors/neoplasia, cancer, colorecta! cancer, brain cancer, bone cancer, epithelial call-derived neoplasia (epithelial carcinoma), basal cell carcinoma, adenocarcinoma, gastrointestinal cancer, lip cancer, mouth cancer, esophagea! cancer, small bowel cancer, stomach cancer, colon cancer, liver cancer, bladder cancer, pancreas cancer, ovarian cancer, cervical cancer, lung cancer, breast cancer, skin cancer, squamus cell and/or basal cell cancers, prostate cancer, renal cell carcinoma, and other known cancers that affect epithelial cells throughout the body; leukemia; lymphoma; systemic lupus erthrematosis (SLE); angiogenesis including neoplasia; metastasis; central nervous system disorders, central nervous system disorders having an inflammatory or apoptotic component, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal cord injury, and peripheral neuropathy; Canine B-Cell Lymphoma. Compounds of the invention are also useful for preventing the production or expression of cyclooxygenase-2, or cyclooxygenase-2 activity. In this aspect, the invention encompasses methods of treating a p38 kinase or TNF-alpha mediated disorder comprising administering to a patient in need thereof a ..he_= t_cal!v effective amount of Compounds according _. .imen i and at leas5 one ona_ma_eu _ ac--r o-- carrier, adjuvant, solvent or excipient. Representative compounds of the invention are: i-benzyl-4- (benzyloxy) -3-b omcpy__ ° din2 ( " H) -one; 2-bromo-!- (4-fiuorobenzy!) -4- [(4fluorobenzy!) oxy] pyridin-2 (IH) -one ; 3-bromo-4- [(2,4-difluorobenzyl)oxy]-l- (2,6dime hylphenyl) - 6-methy!pyridin2 (IH) -one ; 4- (benzyloxy) - 3-bromoI- (4 - fluorobenzyl) pyridin2 (IH) oze ; 3-bromo-4- [(2,4-dif!uorobenzyl)oxy]-l- (3 fluorobenzyl) pyridin2 (IH) -one ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-i- (pyridin3 -ylme hyl) pyridin-2 (IH) -one ; 4-bromo-2- (2,6-dichlorophenyl)-5- [ (2,4dif!uorobenzyl) oxy] pyridazin-3 (2H) -one ; 3-bromoi- (2,6-dichlorophenyl) -4- [ (2,4dif luorobenzy!) oxy] -6-methylpyridin2 (IH) -one ; 3-bromo-l- (3-fluorobenzyl)-4- [ (3~ methylbenzyl ) oxy] pyridin2 (IH) -one ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methylI- (pyridin4 -ylmethyl ) pyridin2 (IH) -one ; 4 - (benzyloxy) - 3 - bromo1 - ( 3 - fluorobenzyl ) pyridin2 (IH) one ; 1 -benzy1-4 - (benzyl oxy) - 3 -bromo6 -methylpyridin-2 (IH) 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -i- (2-methoxy-6methylphenyl ) - 6 -methylpyridin2 (IH) -one ; 3-bromo-4- [ (2,4-difluorobenzyl)oxy]-l-(2fluorobenzyl) pyridin2 (IH) -one ; 3-bromo-4- [ (4fluorobenzyl) oxy] -6-methyli- (pyridin-3y!methy!)pyridin-2 IH) -one; 3-bromo- !- (2,6-dichlorophenyl) -4- [ (4f!uorobenzy!) oxy] methylpyridin-2 (IH) -one ; 4- (benzy!oxy) -3-promoI- (4-methyibenzyl)pyridin-2 (IH) - one ; 4- (benzyloxy) - 3-bromoI- (4-ch]orobenzy!)pyridin-2 (IH) - one; 3-bromo-4- [(2,4-dif!uorobenzyl)oxy]-l- (3methoxvbenzy!) pyridin2 (IH) -one : 4 - { [4- (benzyloxy) - 3-bromo-2-oxopyridin- ! (2H) - y!]methyl)benzoic acid; 4 - (benzyloxy) - 3-bromoi- (2f!uorobenzyl) pyridin2 (IH) - one ; 3-bromoI- (2,6-dimethylphenyl) -4- [ (4fluorobenzyl) oxy] - methylpyridin-2 (IH) -one ; 4- (benzyloxy) -3-bromoi- [4- (methylthio) benzyl] pyridin2 (!H)-one; l-benzyl-4- (benzyloxy) -3-chloropyridin-2 (IH) -one ; 4- { [4- (benzyloxy) - 3-bromo-2-oxopyridin-I (2H) -yl] methyl} N' - hydroxybenzenecarboximidamide ; methyl 4-{ [4- (benzyloxy)-3-bromo-2-oxopyridin-l(2H) - yl] methyl}benzoate ; 3-bromo-4- [ (3-chlorobenzyl)oxy] -i- (3f luorobenzyl ) pyridin2 (IH) - one ; 3-bromo-l- (3-fluorobenzyl) -4- [ (4- fluorobenzyl) oxy] pyridin-2 (IH) -one; 4- { [4- (benzyloxy) -3-bromo-2-oxopyridin-i (2H) - yl ] methyl ) benzoni tri le ; 4- (benzyloxy) -3-bromoI- (2,6-dichlorophenyl) - 6methylpyridin2 (IH) -one ; 3-bromo-4- [ (4fluorobenzyl) oxy] - I- (pyridin-4ylmethyl ) pyridin2 (IH) -one ; 4- (benzyloxy)-3-bromo-I- (4-bromobenzyl)pyridin-2 (IH)-one; y!] methy! }benzonitrile ; !- (3f!uorobenzyl) -4- [ (4-fluorobenzy!) cxy] -3iodopvriiin2(!H)-one; 4-bromo-2- (2,6-d:chloropheny!)-5-{ [2- {hydroxymethy! ) benzyl ] cxy}pvridazin-3 (2H) -one ; 3-bromo-4- [(4-fluorobenzyl)oxy]-i- (pyridin-3ylmethyl) pyridin2 (IH) -one ; 3-bromo-l- (2,4-dif!uorobenzy!)-4- [(2,4dif!uorobenzyl)oxy]pyridin-2 (IH) -one; 3 -bromo-4 - [ (4 - fluorobenzyl) oxy] -6-methylI- (pyridin2 - ylmethyl)pyridin-2(iH)-one; or a pharmaceutically acceptable salt thereof. Embodiment 57. Compounds according to embodiment 1 or embodiment A!, which is 3-bromo-4- [ (4-ch!orobenzyl) oxy] -I- (4fluorobenzyl)pyridin-2 (IH) -one; l-benzyl-3-bromo-4- [ (4-chlorobenzyl)oxy]pyridin-2 (IH) - one ; 3-bromo-l- (4-chlorobenzyl)-4- [(4chlorobenzyl ) oxy] pyridin2 (IH) -one ; 3-bromo-4- [ (4-chlorobenzyl)oxy]-I- [2- (phenylthio) ethyl ] pyridin2 (IH) -one ; 3-bromo-4- [ (4-chlorobenzyl) oxy] -I- (2-phenylethyl) pyridin2 (IH)-one; 3 -bromo4 - hydroxy1 - (4 hydroxybenzyl ) pyridin2 (IH) -one ; 4 - (benzyloxy) - 3 -bromo1 - (piperidin3 -ylmethyl ) pyridin2 (IH) -one hydrochloride; 3 -bromo1 - ( 4 -methoxybenzyl ) - 4 -phenoxypyridin2 (IH) -one ; 1 -benzy1-2 - oxo4 - phenoxyi, 2 - dihydropyridine3 - carbaldehyde ; 3-bromo-4- [ (4-chlorobenzyl) ox -i- (4methoxybenzyl) pyridin2 (!H) -one ; 3-bromo-4- [ (4-fluorobenzyl) oxy] -I- (3phenylpropyl) pyridin-2 (IH) -one; 4- (benzyloxy) - I- [4- (benzy!oxy) benzyl ] - 3-bromopy'-'idzn2 (!H)-one; 4- (benzyloxy) -3-bromoI- [2- (tri f!uoromethyl) benzyl ] pyridin2 (IH) -one ; 4-(benzyloxy)-3-bromo-l- [3- (trifluoromethyl) benzyl ] pyridin-2 (!H) -one ; 4- (benzyloxy) -3-bromo-l- (piperidin-4-y!methyl) pyridin2 (IH)-one hydrochloride; l-benzyl-3-bromo-4-{ [2- (trif!uoromethyl) benzyl] oxy)pyridin-2 (IH) -one ; l-benzy!-4- [ (2,6-dichlorobenzyl) oxy] pyridin-2 (IH) -one ; l-benzyl-4- (benzyloxy)-3- (hydroxymethyl)pyridin-2 IH) - one ; I -benzyl3 -bromo4- [ (2,6-dichlorobenzyl) oxy] pyridin2 (IH) -one; l-benzyl-4- [ (3-chlorobenzyl) oxy] -6-methylpyridin-2 (IH) - one ; 1 -benzyl - 3 - bromo4 - [ (3 - chlorobenzyl ) oxy] - 6 - methylpyridin2 (IH) -one; 1 -benzy1-3 -bromo4 - [ (2 -chlorobenzyl ) oxy] pyridin-2 (IB9 ~ one ; 4- (benzyloxy) -3-bromo-l-ethylpyridin-2 (IH) -one ; 4- (benzyloxy) -I- (4-bromobenzyl) pyridin-2 (IH) -one ; 3 -bromo1 - ( 4 -met hylbenzyl ) - 4 - [ (4 - met hylbenzyl ) oxy] pyridin2 (IH) -one ; methyl 4-{ [4- (benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl] methyl}benzoate; 4- (benzyloxy) -3-bromo-l- (2-thien-3-ylethyl)pyridin-2 (IH) - 4- (benzyloxy)-3-bromo-!- (2-thien-2-ylethyl)pyridin-2 {IH)- one ; l-benzy!-4- [ (3-chiorobenzy!) oxy] py'_-id=n-2 (IH) -one 3-bromo-!- (4fluorobenzy!) -4- [(4f !uorobenzy!) cxy] pyridin2 (!H) -one ; 4- (benzy!oxy) - i- (3f!uorobenzy! ) pyridln2 < IH) -one 4- (benzy!oxy) - !- (2fluorobenzyl) pyridin2 (!H) -one 4- (benzyloxy) - 3-bromo- !-methy!pyridin-2 (IH) -one hydrobromide ; 4- (benzyloxy) - 3-bromol-methylpyridin2 (IH) -one ; 3-bromo-l- (3-chlorobenzyl)-4- [(4chlorobenzyl) oxy] pyridin2 (IH) -one ; 3-bromo-l- (3-chlorobenzyl)-4- [(4fluorobenzyl) oxy] pyridin-2 (IH) -one; 4- (benzyloxy) - I- (4-chlorobenzyl) pyridin2 (IH) -one ; 4- (benzyloxy) - 3-bromoi- [4- (trifluoromethoxy)benzyl]pyridin-2 (!H)-one; 4- (benzyloxy) - 3-bromoi- (4ter -butylbenzyl) pyridin2 (IH) -one; l-benzyl-4 - (benzy!oxy) -6-methy!pyridin-2 (IH) -one ; 1 -benzy1-4 - (benzyloxy) - 3,5 - dibromo6 - methylpyridin2 (IH) one; 4- (benzyloxy) -3-bromo-l- [4- (trifluoromethyl) benzyl] pyridin-2 (IH) -one ; l-benzyl-4- [ (2-chlorobenzyl) oxy] pyridin-2 (IH) -one ; i- (2-bromobenzyl) -3- [ (2-bromobenzyl) oxy] pyridin-2 (IH) - one; methyl 5-chloro-l-(4-ch!orobenzyl)-6-oxo-l,6dihydropyridine-3-carboxylate; 3-benzyl-4-hydroxy-l-(2-phenylethyl)pyridin-2(iH)-one; 5-bromo-!-(2-chloro-6-fluorobenzyl)-3-methylpyridinI- (2-bromobenzy!) -3- [ (2-bromobenzy!) oxy]pyridin-2 (IH) - one; l-benzyl-4- (benzyloxy) pyridin-2 (!H) -one; !-benzyl-4- (benzyloxv) -3-bromopyridin-2 (!H) -one ; l-benzy!-4- (benzy!ox-y) -2-oxoI, 2-dihydropyridine-3carba!dehyde ; l-benzyl-4-chloro2-oxo-!, 2-dihydropyridine3- carbaldehyde ; !-benzyl-4-hydroxy-2-oxo1,2-dihydropyridine3- carba!dehyde ; 1 - benzyl - 4 - (benzyloxy) - 3 -methy!pyridin2 (!H) - one ; 4- (benzyloxy) -i- (4-f!uorobenzy!) pyridin-2 (IH) -one ; l-benzyl-4- (benzyloxy) -3,5-dibromopyridin-2 (IH) -one; 4- (benzyloxy)-3-bromo-l- [4-(methylthio)benzyl]pyridin- 2 (IH)-one; 4 - (benzyloxy) -3-bromoi- (4fluorobenzyl) pyridin2 (IH) - one ; l-benzyl-4- (benzyloxy) -3-chloropyridin-2 (IH) -one ; 3-bromo-l- (4-fluorobenzyl)-4- [(4- f luorobenzyl) oxy] pyridin-2 (IH) -one ; 1 - benzyl - 3 - bromo2 - oxoI, 2 - di hydropyridi n4 - yl methyl phenyl) carbamate ; 1 -benzy1-3 -bromo4 - (2 -phenyl ethyl ) pyridin2 (IH) -one ; 1 -benzyl - 3 -bromo - 4 - ( 3 -phenylpropyl ) pyridin2 ( 1 H) - one ; 1 -benzy1-3 -methyl -4 - (2 -phenyl ethyl ) pyridin2 (IH) -one ; 1 -benzyl - 3 -methyl - 4 - ( 9 -phenylpropyl ) pyridin2 (IH) - one ; 1 -benzy1-4 - (benzyl thio) - 3 -methylpyridin2 (IH) -one ; 1 -benzy1-4 - (benzylthio) -3 -bromopyridin2 (IH) -one ; 1 -benzy1-2 -oxoI, 2 -dihydropyridin4 -yl methanesul fonate 3 - acetyl - 4 -hydroxy6 -methyl - 1 - [ choro ] phenylpyridin2 (IH) one; 6-(benzyloxy)-l-methyl-2-oxo-l,2-dihydropyridine-3carbonitrile; 3-benzoy!-6- (benzyloxy) - !-methylpyridin-2 (IH) -one; 3-benzyl-6- (benzyloxy) - !-methylpyridin-2 (IH) -one ; l-benzyl-4-hydroxyPyrldin-2 (!H) -one ; l-benzyl-4- (benzylthio) pyridin2 (IH) -one 4-aminol-benzy!pyridin-2 (IH) -one ; l-Denzy!-4- (benzyloxy) pyridin-2 (!H) -one ; l-Denzy!-4-hydrox}qpyridin2 (IH) -one ; 1 -benzyl - 2 -oxoi, 2 - dihydropyr idin - 4 -y! methyl (phenyl) carbamate ; or a pharmaceutically acceptable thereof. Embodiment 58. Compounds according to embodiment embodiment AI, which is 4- (benzyloxy) -I- (4-methylbenzyl) pyridin-2 (IH) -one; 4 - (benzyloxy) -3 -bromopyridin2 I IH) - one ; methyl 4-{ [4- (benzyloxy)-2-oxopyridin-i (2H) -yl]methyl} benzoate ; methyl -4- { [4- (benzyloxy) - 3-bromo2-oxopyridin1 (2H) - yl]methyl} benzoate; 4- { [4- (benzyloxy) -2-oxopyridin-I (2H) -yl] methyl } benzonitrile ; 4- (benzyloxy) -i- (4tert-butylbenzyl) pyridin-2 (IH) -one 4- (benzy!oxy) -i- [4- (trifluoromethyl) benzyl] pyridin-2 one ; 4- (benzyloxy) -3-bromoi- [4- (trifluoromethyl) benzyl ] pyri di n2 ( 1 H) - one ; 4- (benzyloxy) -3-bromo-l- [3- (trifluoromethyl) benzyl]pyridin-2 (IH) -one ; 4 - (benzyloxy) - 3 -bromo1 - [2 - ( tri fluoromethyl ) benzyl ] pyridin-2 (IH) -one ; 4- (benzyloxy) -1- [4- (trifluoromethoxy) benzyl ] pyridin4 - (benzyloxy) - 3 -bromo- ! - [4 - ( tri fluoromethoxy) benzy!] pyridin-2 (IH) -one; i-benzyl-4-hydroxy6-methy!pyridln-2 (IH) -one ; !-benzy!-6-methyl-2-oxo-l, 2-dihydropyridin-4 -yl 4 - bromobenzenesul fona t e ; !-benzyl-3-bromo-4- [ (3-chlorobenzy!) oxy] - 6-methvlp.vridin2 (IH) -one; !-benzy!-6-methyi-2-oxoI, 2-dihydropyridin-4-yl 4 - bromobenzenesul fonat e ; !-benzyl-3-bromo-4- [ (3-chlorobenzyl) oxy] -6-methy!pyridin2 (IH) -one; l-Benzyl-4- [2,6- (dichlorobenzyl) oxy] pyridin2 (IH) -one ; 4- [ (2,6-dichlororbenzyl) oxy] pyridinel-oxide ; 4- [(2,6-dichlorobenzyl)oxy]pyridine 1-oxide; l-Benzyl3-bromo-4- [2,6- (dichlorobenzyl) oxy] pyridin2 (IH) -one; !-Benzyl3-bromo4- [ (4-methylbenzyl) oxy] pyridin-2 (IH) - one; l-Benzyl-4- -3-bromopyridin-2 (IH) -one; l-benzyl-4- (benzyloxy) -3-iodopyridin-2 (IH) -one ; 1 -benzyl -4 - (benzyloxy) - 3 -vinylpyridin2 (IH) -one ; 1 - benzyl - 4 - (benzyloxy) - 3 -ethylpyridin2 (IH) -one ; 3-acetyi-4- (benzyloxy) -I- (2-chlorophenyl) -6methylpyridin2 (IH) -one ; 3 - acet yl - 1 - ( 2 - chlorophenyl ) - 4 - hydroxy6 - met hylpyridin2 (iH)-one; 1 - benzyl - 3 - bromo4 - hydroxypyr i din - 2 ( IH ) - one ; 1 - benzyl - 3 -bromo2 -oxoi, 2 - dihydropyridin4 -yl t r i f I uorome thane sul f onat e ; l-benzy1-3 -bromo4 - (phenylethynyl) pyridin2 (IH) -one ; 3-bromo-l- (3-fluorobenzyl)-6-methyl-4-(2phenylethyl) pyridin-2 (IH) -one ; 1 - (3 - fluorobenzyl ) -4 - hydroxy6 - methylpyridin2 (IH) -one ; 3-bromo-l-(3-fluorobenzyl)-4-hydroxy-6-methy!pyridin2 iH)-one; 3-bromo-l-(3-fluorabenzyl)- -me_Av= " - -2oxo1,2dihydropyridin-4-yl - =: u_ luo_ome h_nesu = . .... f na'e ; 3-bromo-i-(3-fiuorobenzyl)-6-methyl-4- (phenylethynyi)pyridin-2(IH)-one; 3-acetyl-l- (2,6-dichloropheny!)-4-hydroxy-6methylpyridin-2(IH)-one; !-(2,6-dichlorophenyl)-4-hydroxy-6-methylpyridin-2(iH)- one ; 4-(benzyloxy)-l-(2,6-dichlorophenyl)-6-methylpyridin2 iH)-one; 3-bromo-l-(3-f!uorobenzy!)-4-(2-phenylethy!)pyridin2 iH)-one; 3-bromo-l-(3-f!uorobenzyl)-4-hydroxypyridin-2(IH)-one; 3-bromo-l-(3-fluorobenzyl)-2-oxo-!,2-dihydropyridin-4-yl trif!uoromethanesulfonate; 3-bromo-l-(3-f!uoroben=yl)-4-(phenylethynyl)pyridin2(iH)-one; 4-(benzyloxy)-3-ethynyl-l-(3-fluorobenzyl)pyridin-2(IH)- one; 4-(benzyloxy)-l-(3-fluorobenzyl)-3-iodopyridin-2(IH)-one; 4-(benzyloxy)-l-(3-fluorobenzyl)-3- [(trimethylsilyl)ethynyl]pyridin-2(iH)-one; 4-(benzylamino)-3-bromo-l-(3-fluorobenzyl)pyridin-2(iH)- one ; l-(3-fluorobenzyl)-4-hydroxypyridin-2(IH)-one; 4-(benzylamino)-l-(3-fluorobenzyl)pyridin-2(iH)-one; or a pharmaceutically acceptable salt thereof. Embodiment 59. Compounds according to embodiment 1 or embodiment AI, which is fluorobenzy!) pyridin-2 (!H) -one; 3-bromo-4- [(4-fluorobenzy!)oxy]-6~methy!-!- (pvridin- - ylme hyl) pyridin-2 (IH) -one ; 3-bromo-4- [ (4fluorobenzyl) oxy] -6-methyl- !- (pyri/in-4ylmethyl) pyridin-2 (IH) -one ; 3-bromoI- (2,6-dichlorophenyl) -4- [ (4 -fluorobenzy! ) o×y] -6methv!pyridin-2 (IH) -one ; 3-bromo-4- [ (2,4-dif!uorobenzyl) oxy] -I- (3- methoxybenzyl)pyridin-2 (114) -one; 3-bromoI- (2,6-dimethylphenyl) -4- [ (4f!uorobenzy!) oxy] -6methylpyridin-2 (IH) -one ; 3-bromo-4- [ (3-chlorobenzyl)oxy]-!- (3fluorobenzyl) pyridin2 (IH) -one; 3 -bromo-4 - [ (4 - fluorobenzyl ) oxy] - 1 - (pyridin4 - ylmethyl) pyridin2 (IH) -one ; 3-bromo-!- (3-fluorobenzyl) -4- [ (4fluorobenzyl) oxy] pyridin-2 (IH) -one; 4- { [3-bromo-4- [ (4fluorobenzyl) oxy] -2-oxopyridin1 (2H) - yl] methyl }benzonitrile ; 1 - ( 3 - f luorobenzyl ) - 4 - [ ( 4 - f luorobenzyl ) oxy] - 3 - iodopyridin2 (IH) -one; 3 -bromo4 - [ (4 - fluorobenzyl ) ox-y] - 1 - (pyridin-3 - ylmethyl ) pyridin2 (IH) -one ; 3-bromo-l- (2,4-difluorobenzyl)-4- [(2,4di fluorobenzyl ) oxy] pyridin2 (IH) - one ; 3 -bromo4 - [ (4 - f luorobenzyl ) oxy] - 6 -methyl - 1 - (pyridin2 - ylmethyl ) pyridin2 (IH) -one ; 3-bromo-4- [(2,4-difluorobenzyl)oxy]-l- (3- fluorobenzyl) pyridin-2 (IH) -one; dif!uorobenzyl) oxy] -6-methylpyridin-2 (!H) -one; 3-bromo-l- (3-f!uorobenzy!)-4- [(3methy!benzy!) oxy] piperidin2-one; 3-bromo-4- [ (2,4-dif!uorobenzyi) oxy] -6-methyiI- (pvridin4-ylmethyl) pyridin-2 (!H) -one ; 3-bromo-4- [ (2,4-dif!uorobenzyl) oxy] - i- (2-methoxy6- methyiphenyl) - 6-methylpyridin-2 (IH) -one ; or a pharmaceutically acceptable salt thereof. Embodiment 60. Compounds according to embodiment i, which is I- (!-acetyl-2,3-dihydro-iH-indol-5-yl)-3-chloro-4- [ (2,4difluorobenzyl) oxy] -6-methylpyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl } oxy] - I- (l-glycoloyl-2,3dihydroIH-indo!- 5-yl) - 6-methylpyridin-2 (IH) -one ; 3-chloro-4- [(2,4-difluorobenzyi)oxy]-l- [I- (2-hydroxy-2menhylpropanoyl) -2,3-dihydroIHindol5-y! ] - 6-methy!pyridin2(IH)-one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - 6-methylI- [ I- (Nmethylglycyl) -2,3-dihydroiH-indol5-yl ] pyridin-2 (1H) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- [i- (3hydroxypropanoyl ) -2,3 - dihydroIHindol - 5-yl ] - 6 -methylpyridin2 ( 1 H) - one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- [i- (3-hydroxy-3me t hylbut anoyl ) - 2,3 - dihydroIHindol - 5 -yl ] - 6 - methylpyr idin2 (IH) -one; 5- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyr idin1 (2 H) -yl ] indol ine1 - carboxamide ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [l- (methylsulfonyl) -2,3-dihydroiH-indol5-yl] pyridin-2 (IH) -one ; di f luorobenzyi ) oxy] - 6 -methylpyridin2 (IH) -one ; 3-chloro-4- [(2,4-difiuorobenzy!)oxy]-!- (l-glycoloyl-iH~ indo!-5-yl) -6-methylpyridin-2 (!H} -one; 3-ch!oz-o-4- [(2,4-difluorobenzyl)oxy]-l- [i- (2-hydroxy-2- methylpropanoyl) - !H-indol-5-yl] -6-methylpyridin-2 (IH) -one; 3-chloro-4- [(2,4-dif!uorobenzyl)oxy]-6-me-hy!-i- [I- (Nmethy!glycyl) -iH-indol5-yl] pyridin-2 (IH) -one; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l- [i- (3hydroxypropanoyl ) - !Hindol5-yl ] - 6-methylpyridin2 (IH) -one ; 3-ch!oro-4- [(2,4-difluorobenzyl)oxy] -i- [i- (3-hydroxy-3methylbutanoyl) - IH-indol5-yl] - 6-methylpyridin2 (IH) -one; 5- [3-chloro-4- [ (2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl] - iH~indolel-carboxamide ; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-6-methyl-l- [i- (methyisulfonyl)-iH-indol-5-yl]pyridin-2(iH)-one; I- (2-acetyl-2,3-dihydroiH-isoindol5-yl) - 3-chloro-4- [(2 0 4-difluorobenzyl)oxy] -6-methylpyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - I- (2-glycoloyl-2,3 - dihydroIHisoindol5-yl) - 6-methy!pyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- [2- (2-hydroxy-2methylpropanoyl ) - 2 , 3 - dihydroIHi soindol - 5 -yl ] - 6methylpyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [2- (Nmethylglycyl ) -2,3 -dihydroIHi soindol - 5 - yl ] pyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- [2- (3hydroxypropanoyl ) - 2,3 - dihydroIHisoindol - 5 -yl ] - 6 - methylpyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i~ [2- (3-hydroxy-3methy!but anoyl ) - 2,3 - dihydro - IHisoindol - 5 -yl ] - 6 - methylpyridin- 2 (IH) -one; 5- [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin1 (2H) -yl] - 1,3 - dihydro2Hisoindole-2 - carboxamide ; (methylsulfonyl) -2,3-dihydro- !H-isoindol5-vl] pvridin2 (IH) i- (2-acetyli, 2, 3,4 - -e rahydroisoquino!ln-6-yi) -3 -chioro- 4- [ (2,4-difluoroben=yl)oxy] - 6-methylpyridin-2 (!H) -one; 3-chloro-4- [(2,4-difluorobenzyi)oxy]-!- (2-glyccloyl1,2,3,4-tetrahydroisoquino!in-6-y!)-6-methylpyridin-2 (-H) -cne; 3-chloro-4- [(2,4-difiuorobenzyl)oxy] -i- [2- (2-hydroxy-2methylpropanoyl) - 1,2,3,4 - te rahydroisoquinoiin6-y! ] - 6- m thylpyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl)oxy]-6-methyl-!- [2- (Nmethylglycyl) - I, 2,3,4-tetrahydroisoquinolin-6-yl] pyridin2 (IH) -one; 3-ch!oro-4- [(2,4-difluorobenzyl)oxy]-l- [2- (3- hydroxypropanoyl) -i, 2,3,4tetrahydroisoquinolin6-yl] -6methylpyridin2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzy!)oxy]-l- [2- (3-hydroxy-3methylbutanoyl) - 1,2,3,4tetrahydroisoquinol in6- yl] -6methylpyridin-2 (IH) -one ; 6- [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin-i (2H) -yl] -3,4-dihydroisoquinoline-2 (IH) - carboxamide ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [2- ( methylsul fonyl ) - I, 2,3,4 - t et rahydroisoquinol in6 - yl ] pyridin 2 (IH) -one; I- (2-acetyl-l, 2,3,4-tetrahydroisoquinolin-7-yl) -3-chloro4- [ (2,4-difluorobenzyl) oxy] -6-methylpyridin2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -i- (2-glycoloylI, 2,3,4-tetrahydroisoquinolin-7-yl) -6-methylpyridin-2 (iN) -one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- [2- (2-hydroxy-2methylpropanoyl) - I, 2,3,4tetrahydroisoquinolin7-yl] -6methylpyridin2 (IH) -one ; methylglycy!) -i, 2,3,4-tetrahydroisoquino!in7-yl] pyridin2 (iH)-one; 3-chloro-4f(2,4-difluorobenzylloxy]-l12-13hydroxypropanoy!) -I, 2,3,4-tetrahydroisocfuinolin-7-y!] - 6meth}'Ipyridin-2 (IH) -one ; 3-chloro-4- [(2,4-dif!uorobenzyl)oxy]-!- [2- (3-hydroxy-3methylbutanoyl) - 1,2,3,4-tetrahydroisoquinolin-7-v!] -6menhy/pyridin2 (IH) -one ; 7- [3-ch!oro-4- [ (2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl] -3,4-dihydroisoquino!ine-2 (IH) - carboxamide ; 3-chloro-4- [(2,4-difluorobenzy!)oxy] -6-methyl-l- [2- (methylsulfonyl) - i, 2,3,4-tetrahydroisoquinolin7-yl] pyridin2 IH) -one; I- (!-acetyl-IH-benzimidazol-5-y!)-3~chloro~4- [ (2,4di f luorobenzyl) oxy] -6-methylpyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - I- (l-glycoloyl-iHbenzimidazol5-yl) -6-methylpyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -I- [I- (2-hydroxy-2methylpropanoyl ) - iH-benzimidazol - 5-yl ] - 6 -methylpyridin2 (IH) one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [i- (Nmethylglycyl ) - IHbenzimidazol - 5 - yl ] pyridin2 (IH) - one ; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -i- [i- (3hydroxypropanoyl ) - iH-benzimidazol - 5 -yl ] - 6 -methylpyridin2 (1/4) one ; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -I- [I- (3-hydroxy-3methylbut anoyl ) - iH-benzimidazol - 5 -yl] - 6 -methylpyridin2 (IH) - one ; 5- [3-chloro-4- [ {2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl] - iH-benzimidazolel-carboxamide ; (methylsulfonyl) - !H-benzimidazo!- 5-vl ] pvridin2 (1H) -ene ; 3-chiore-I- (l,3-diacetyi-2,]-dihvdro-!H-benzimidazol-< yl)-4-[(2,4-dif!uorcbenzy!)oxy]-6-meshylpyrzdln-2(!H]-one; l-(3-acetyl-l-glycoloy!-2,3-dihydro-iH-benzlmidaze!-5yl)-3-chloro-4-[(2,4-dif!uorobenzyl)oxy]-6-mezhy!pyrilin2(!H)-one; l-[3-acetyl-l-(2-hydroxy-2-methylpropanoyl)-2,3-dihydroiH-benzimzdazol-5-yl]-3-chloro-4-[(2,4-dzf!uorobenzyl}oxy]-6- me hylpyridin-2(IH)-one; l-[3-acetyl-l-(N-methy!giycyl)-2,3-dihydro-iHbenzimidazol-5-yl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(iH)-one; l-[3-acetyl-l-(3-hydroxypropanoyl)-2,3-dihydro-iH- benzimidazol-5-yl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(iH)-one; l-[3-acetyl-l-(3-hydroxy-3-methy!butanoyl)-2,3-dihydroIH-benzimidazol-5-yl]-3-chloro-4- [(2,4-difluorobenzyl)oxy]-6methyipyridin-2(iH)-one; 3-acetyl-5-[3-chloro-4-[(2,4-difluorobenzy!)oxy]-6methyl-2-oxopyridin-l(2H)-yl]-2,3-dihydro-IH-benzimidazole-lcarboxamide; l-(l-acetyl-3-glycoloyl-2,3-dihydro-IH-benzimidazol-5yl)-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin- 2(iH)-one; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-(l,3-diglycoloyl2,3-dihydro-iH-benzimidazol-5-yl)-6-methylpyridin-2(iH)-one; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-[3-glycoloyl-l-(2hydroxy-2-methylpropanoyl)-2,3-dihydro-iH-benzimidazol-5-yl]- 6-methylpyridin-2(iH)-one; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-[3-glycoloyl-l-(Nmethylglycyl)-2,3-dihydro-iH-benzimidazol-5-yl]-6methylpyridin2 (IH)-one; 3-ch!oro-4- [(2,4-dif!uorobenzyl)oxy]-!-[3-gl¥cc!oyi-l- (3hydroxypropanoy! ) - 2,3-dihydro-iH-benzimidazol-5-yl]-6methylpyridin-2 (IH)-o e; 5-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methy!-2oxopyridin-l(2H)-yl]-3-glycoloyl-2,3-dihydro-IH-benzimidazo!el-carboxamide; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l- [3-glycoloyl-l- (3hydroxy-3-methylbutanoyl)-2,3-dihydro-!H-benzimidazol-5-yl]-6- methy!pyridln-2(iH)-one; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-[3-gl¥coloyl-l- (methylsulfonyl)-2,3-dihydro-IH-benzimidazol-5-yl]-6methylpyridin-2(iH)-one; l-[l-acetyl-3-(2-hydroxy-2-methylpropanoyl)-2,3-dihydro- IH-benzimidazol-5-yl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(IH)-one; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l- [l-glycoloyl-3-(2hydroxy-2-methylpropanoyl)-2,3-dihydro-iH-benzimidazol-5-yl]- 6-methylpyridin-2(iH)-one; l-[l,3-bis(2-hydroxy-2-methylpropanoyl)-2,3-dihydro-IHbenzimidazol-5-yl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(iH)-one; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-[3-(2-hydroxy-2methylpropanoyl)-l-(N-methylglycyl)-2,3-dihydro-iH- benzimidazol-5-yl]-6-methylpyridin-2(IH)-one; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-[3-(2-hydr0xy-2methylpropanoyl)-l-(3-hydroxypropanoyl)-2,3-dihydro-iHbenzimidazol-5-yl]-6-methylpyridin-2(iH)-one; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-[l-(3-hydroxy-3- methylbutanoyl)-3-(2-hydroxy-2-methylpropanoyl)-2,3-dihydroiH-benzimidazol-5-yl]-6-methylpyridin-2(IH)-one; oxopyr din1 (2H) -yl] -3- (2-hydroxyl-2-methy!propanoyl) -2,3dihydroIHbenzimi dazole- ! - carboxamide ; 3-cn_o_o-4-' [ (2,4-dif-uorobenzvi oxy]-!. - [3- (2-hydroxy-2methy!propanoyl) - I- (methylsu!f0nyl) -2,3-dihydroIHbenzimidazol5-yi] -6-me:hyipyridin-2 (!H) -one ; - If-ace-y!-3-(l{-meth¥1glycy!)-2,3-dihydro-iHbenzimidazol-5-yl]-3-chlcro-a.- (2,4-difiuorcbenzyl)ox?] -6methy!pyridin-2 (IH) -one ; 2-chioro-4- [(2,4-dif!uoro enzyl)oxy]-ii-glycoloy!-3- (Nmeth¥!glycyi) -2,3-dihydroIH-benz!midazol5-vl ] - 6methylpyridin-2 (IH) -one ; 3-chloro-4- [(2,4-dif!uorobenzyl)oxy] -i- [I- (2-hydroxy-2methylpropanoyl) -3- (N-methy!glycyl) -2,3-dihydroIHbenzimidazol5-yl] - 6-methylpyridin-2 (IH) -one ; i- [I, 3-bis (N-methylg!ycyl) -2,3-dihydroiH-benzimidazol-5yl]-3-chloro-4- [(2,4-difluorobenzyi)oxy]-6-methylpyridin2(IH) -one; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l- [!-(3hydroxypropanoyl } - 3 ~ (Nme chyl gl ycyl ) - 2,3 - d i hydro - IHbenzimidazol-5-yl] -6-methylpyridin-2 (iH)-one; 3 -chloro-4- [ (2,4 -difluorobenzyl ) oxy] - 1 - [ i- (3-hydroxy-3methylbutanoyl) -3- (N-methylglycyl) -2,3 -dihydroIHbenzimida zol - 5 - yl ] - 6 - me t hylpyridi n2 (IH) - one ; 5- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) - yl ] - 3 - (N-methylglycyl) - 2,3 - dihydroIHbenzimidazol e - 1 - carboxamide ; 3-chloro-4- [ (2,4 ~dif!uorobenzyl) oxy] -6-methyl-l- [3- (Nmethylglycyl) - i- (methylsul fonyl) -2,3 -dihydroiH-benzimidazol5-yl] pyridin-2 (IH) -one ; 1 - [ 1 - acetyl - 3 - ( 3 - hydroxypropanoyl ) - 2,3 - dihydroIHbenzimidazol5-yl] -3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6methylpyridin-2 (IH) -one ; 3 -chloro4 - [ ( 2,4 -difluorobenzyl ) oxy] - 1 - [I -glyco!oy! - 3 - ( hydroxypropanoyl) -2,3-dihydroiH-benzimidazo!- 5-yl] -6menhyipyridln-2 (IH) -one ; 3-ch!oro-4- [(2,4-difluorobenzyl)oxy]-i- [!- (2-h},droxy-2- methv!propanoy!) -3- (3-hydroxypropanoyl) -2,3-dihydro- !Hbenzimidazol5-y! ] - 6-methylpyridin-2 (!H) -one ; 3-chloro-4- [ (2,4-dif!uorobenzyl)oxy] -i- [3- (3hydroxvpropanoy!) - !- (N-methylg!ycy!) -2,3-dihydroIHbenzimidazol5-yl ] - 6-methylpyridin2 (IH) -one ; !- [i, 3-bis (3-hydroxypropanoy!) -2,3-dihydroIHbenzimidazol-5-yl] -3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6methylpyridin-2 (1H) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -I- [I- (3-hydroxy-3methylbutanoyl) - 3- (3-hydroxypropanoyl) -2,3-dihydro-iH- benzimidazol5-yl] -6-methylpyridin-2 (IH) -one ; 5- [3-chloro-4- [ (2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin- ! (2H) -yi ] - 3- (3-hydroxypropanoyl) -2,3 - dihydroIHbenzimidazolel-carboxamide ; 3-chloro-4- [ (2,4-dif!uorobenzyl)oxy] -I- [3- (3- hydroxypropanoyl) - i- (methylsulfonyl) -2,3-dihydroIHbenzimidazol-5-yl] -6-methylpyridin-2 (IH) -one ; 1 - [ 1 -acetyl - 3 - ( 3 - hydroxy3 - methylbut anoyl ) - 2,3 - dihydroiH-benzimidazol-5-yl] -3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6methylpyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -I- [l-glycoloyl-3- (3hydroxy3 -methylbut anoyl ) - 2,3 -dihydroIH-benz imidazol - 5 -yl ] - methylpyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -I- [3- (3-hydroxy-3methylbutanoyl) - I- (2-hydroxy-2-methylpropanoyl) - 2,3-dihydro- iH-benzimidazol5-yl] - 6-methylpyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- [3- (3-hydroxy-3methylbutanoyl) - I- (N-methylglycyl) - 2,3-dihydroIHbenzimidazol5-yl] -6-methylDyridin-2 (IH) -one; 3-ch!oro-4- [(2,4-dif!uorobenzyl)oxy]-l- [3-(3-hydrcxy-3methylbutanoy!) - i- (3-hydrox} ropanoyl) -2,3-dihydro- !Hben-_imidazol5-y!] -6-methy!pyridin-2 (IH) -one ; !- [ 1,3-bis (3-hydroxy3-methy!butanoyl) -2,3-dihy/roIHben_-imidazol-5-yl] -3-chloro-4- [(2,4-difluorobenzyl)oxv]-6me=hyipyridin-2 (ill) -one; 5- [3-chloro-4- [(2,4-difluorobenzy!)oxy]-6-methyl-2oxopyridin1 (2H) -yl] -3- (3-hydroxy3-methylbutanoyl) -2,3- dihydroiH-ben:imidazolel-carboxamide ; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l- [3- (3-hydroxy-3methy!butanoyl) - I- (methylsulfonyl) -2,3-dihydroIHbenzimidazol-5-yl]-6-methylpyridin-2 (iH)-one; 3-acetyl6- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6- methyl-2-oxopyridin-I (2H) -yl] -2,3-dihydro-IH-benzimidazole-lcarboxamide ; 6- [3-chloro-4- [(2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin1 (2H) -yl ] -3-glycoloyl -2,3-dihydroiH-benzimidazole- ! - carboxamide ; 6- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl2- oxopyridin-I (2H) -yl] -3 - (2 -hydroxy-2 -methylpropanoyl ) -2,3 - dihydroIH-benzimidazole1 - carboxamide ; 6- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl ] - 3 - (N-methylglycyl) - 2,3 -dihydroIH- benzimidazol ei- carboxamide ; 6- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6 -methyl -2oxopyridin1 (2H) -yl] -3- (3 -hydroxypropanoyl ) -2,3 -dihydroIHbenzimidazole1 - carboxamide ; 6- [3-chloro-4- [ (2,4~difluorobenzyl) oxy] -6-methyl-2- oxopyridin-i (2H) -yl] -3- (3-hydroxy-3-methylbutanoyl) -2,3dihydro - IHbenzimida zol e ~ 1 - carboxamide ; oxopyridin- ! (2H) -yl] - IH-benzimidazole-I, 3 (2H) -dicarboxamide ; 6- [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -6-methy!-2oxcpvridin1 (2H) -yl] -3- (methylsulfonyl) -2,3-dihydroIHbenzimidazo!el-carboxamide; !- [l-ace-yl-3-(methylsulfonyl)-2,3-dihydro-IHbenzimidazo!-5-yl]-3-chloro-4- [(2,4-difluoroben=yl)oxy]- - methvlpyridin2 (!H) -one ; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l- [l-glycoloyl-3- (methylsul fonyl ) -2,3-dihydroiH-benzimidazol5-yl ] - 6menhylpyridln-2 (iH)-one; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -i- [I- (2-hydroxy-2methylpropanoyl) -3 - (methylsu! fonyl) -2,3 -dihydroIHbenzimidazol-5-yl] -6-methylpyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyli- [i- (Nmethylglycyl) -3- (methylsulfonyl) -2,3-dihydro- !H-benzimidazol5-y-]pvridin-2 (IH) -one; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l- [l-(3hydroxypropanoyl) - 3- (methylsul fonyl) - 2,3-dihydroIHbenzimidazol5-yl ] -6-methylpyridin-2 (!H) -one ; 3-chloro-4- [ (2,4-dif!uorobenzyl) oxy] -i- [I- (3-hydroxy-3methylbut anoyl ) - 3 - (methyl sul fonyl ) - 2,3 - dihydroIHbenzimidazol-5-yl] -6-methylpyridin-2 (IH) -one; 5- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2OXOlDyridin1 (2H) -yl ] - 3 - (methyl sul fonyl ) - 2,3 -dihydroIHbenzimidazole1 - carboxamide ; I- [I, 3-bis (methylsulfonyl) -2,3-dihydro-iH-benzimidazol-5yl] -3-chloro-4- [ (2,4-difluorobenzyl) oxy] - 6-methylpyridin2 (IH) -one; I- [3-acetyl-l- (methylsulfonyl) -2,3-dihydro-iHbenzimidazol-5-yl] -3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6methylpyridin-2 (IH) -one ; dz f!uorobenzyl) oxy] - 6-methy!pyridin-2 (IH) -one; 3-ch!oro-4- [(2,4-dif!uorobenzy!)exy]-i- (l-g!ycoloy!-iHpyrro!-3-yl) -6-me=hyipyridin-2 (IH) -one; 3-chlcro-4- [(2,4-dif!uorobenzyl)oxy]-l- [i- {2-hydroxy-2- methy!propanoyl)-!H-pyrrol-3-yl] -6-methy!pyrid!n-2 (IH) -one; 3-ch!orc-4- [(2,4-difluorobenzyl)oxy] -6-methyl-l- [i- <Nmethyiglycyl) - iH-pyrro!- 3-yl ] pyridln-2 (IH) -one ; 3-chloro-4- [(2,4-difluorobenzy!)oxy]-!- [l-(3hydroxypropanoyl ) - iH-pyrrol-3-yl ] -6-me hylpyridin-2 (!H) -one 3-chloro-4- [(2,4-difluorobenzyl)oxy] -I- [I- (3-hydroxy-3methylbutanoyl) - iH-pyrrol3-yl] -6-methylpyridin-2 (!H) -one; 3- [3-chloro-4- [ (2,4-dif!uorobenzyl)oxy]-6-methyl-2oxopyridin-I (2H) -y! ] - IH-pyrro!el-carboxamide ; 3-chloro-4- [(2,4-difluorobenzyl)oxy] -6-methyl-l- [i- (methy!sulfonyl)-IH-pyrrol-3-yl]pyridin-2 (IH)-one; l- (i-acetyl-iH-imidazol-4-yl)-3-chloro-4- [(2,4difluorobenzyl ] oxy] - 6-methylpyridin-2 (IH) -one ; 3chloro-4- [ (2,4-difluorobenzyl) oxy] - i- (l-glycoloylIHimidazo!-4-yl)-6-methylpyridin-2 (iH)-one; 3-ch]oro-4- [ (2,4-difluorobenzyl)oxy] -i- [i- (2-hydroxy-2me thylpropanoyl ) - IHimidazol -4 -yl ] - 6 -methylpyridin-2 (IH) -one 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-l- [I- (Nmethylglycyl ) - IHimidazol - 4 -yl ] pyridin2 (IH) - one ; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -i- [i- (3- hydroxy!Dropanoyl ) -IHimidazol-4 -yl] -6-methylpyridin-2 (IH) -one 3 - chl oro4 - [ ( 2,4 - di fluorobenzyl ) oxy] - 1 - [ 1 - ( 3 - hydroxymethylbutanoyl) - iH-imidazol-4-yl] -6-methylpyridin-2 (IH) -one 4- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin-I (2H) -yl ] - IH-imidazole-l-carboxamide; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [l- (methylsulfonyl) -iH~imidazol-4-yl ] pyridin-2 (IH) -one; difluorobenzyl) oxy] -6-methy!pyridin-2 (IH) -one; 3-ch!oro-4I(2,4-difluorobenzyl)oxy]-!- (l-£lycoloyl-!Hpyrazoi-4-yl) - 6-methylpyridin-2 (IH) -one ; 3-chloro-4- [(2,4-difluorobenzyi)oxy]-!- [I- (2-hydroxy-2- methylpropanoyl) -is-pyrazo!-4-yl] -6-methy!pyridin-2(!H) 3-ch!oro-4- [ (2,4-dif!uorobenzy!) oxy] -6-methylmenhylglycyl) - iH-pyrazol-4-yl] pyridin-2 (IH) -one; 3-chloro-4- [ (2,4-dif!uorobenzyl)oxy]-l- [I- (3hydroxypropanoy! ] - iH-pvrazol-4-yl ] - 6-methylpyridin- 3-chloro-4- [(2,4-difluorobenzy!)oxy]-l- [i- (3-hydroxy-3methylbutanoyl) -UH-pyrazol-4-yl] - 6-methylpyridin-2 (IH) 4- [3-chloro-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl] - iH-pyrazoleI- carboxamide ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-]- (methy!sulfonyl)-!H-pyrazol-4-yl]pyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -l-isoquinolin6-methylpyridin2 (IH) -one ; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l- (isoquinolin-6y!methyl) pyridin-2 (IH) -one ; 5- { [3-chloro-4 - [ (2,4 -difluorobenzyl) oxy] -2-oxopyridinI (2H) -yl] methyl }-i, 3-dihydro-2H-indol-2-one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- (2,3-dihydroindol - 5-ylmethyl ) pyridin2 (IH) - one ; i- [ (l-acety1-2,3-dihydro-IH-indo1-5-yl) methyl] 4- [(2,4-difluorobenzyl)oxy]pyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -I- [ (l-glycoloyl-2,3dihydroIHindol - 5 -yl ) methyl ] pyridin2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- { [I- (2-hydroxy-2methylpropanoyl ) - 2,3 -dihydroIHidol - 5 -yl ] methyl } pyri 2 (IH) -one; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l-{ [i- (Nmethylglycyl) -2,3-dihydroIH-indol5-yl] methyl }pyridin-2 3-cln!oro-4- [ (2,4-difiuorobenzyl)oxy] -!- { [!- (3hydroxypropanoyl) - 2,3-dihvdro- !H-indoi5-v! ] methyl }pvridin2 (!H) -one; 3-chioro-4- [(2,4-dif!uorobenzyl)oxy]-l-{ [!- (3-hydroxy-3methy!butanoy!) -2,3-dihydroIHindo!- 5-yl] mezhy! } pyr'_dzn2 (1}4) -one; 5-{ [3-chloro-4- [(2,4-difluorobenzyl)oxy]-2-oxopyridin1 (2H) -yl] methyl } indolinel-carboxamide ; 3-chioro-4- [(2,4-difluorobenzyl)oxy]-i-{ [l- (methylsul fonyl) - 2,3-dihydroIHindol5-yl ] methyl } pyridin2 (iH)-one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- (2,3-dihydro-iHisoindol5-ylmethyl) pyridin2 (IH) -one ; i- [ (2-acetyl-2,3-dihydro-IH-isoindol-5-yl)methyl] -3chloro-4 - [ (2,4-difluorobenzyl) oxy] pyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-dif!uorobenzyl)oxy] -i- [ (2-glycoloyl-2,3dihydroIHisoindol5-yl) methyl] pyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - i- { [2- (2-hydroxy-2- methylpropanoyl ) - 2,3-dihydroIHisoindol - 5-yl ] methyl }pyridin2 (iH)-one; 3~chloro-4- [ (2,4-difluorobenzyl)oxy] -i-{ [2- (Nmethylglycyl) - 2,3 -dihydroIHisoindol - 5 -yl ] methyl } pyridin2 (IH) -one; 3 ~chloro-4- [ (2,4-difluorobenzyl) oxy] -i- { [2- (3hydroxypropanoyl ) - 2,3 -dihydroIHi soindol - 5 -yl ] methyl } pyridin2 (iH)-one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- { [2- (3-hydroxy-3methylbutanoyl ) - 2,3 - dihydroIHiso indol - 5 - yl ] methyl }pyridin- 2 (IH) -one; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] - 2-oxopyridin1 (2H) -yl ] methyl } ~ i, 3 -dihydro-2Hisoindole2-carboxamide ; (methylsul fonyl } -2,3-dihydro-iH-isoindo!-5-yl ] methyl }pyridin2 (IH)-one; 3-chlcro-4-[(2,4-difluorobenzy!)oxy]-l-(!,2,3,4tetrahydroisoquinolin-6-ylmethyl) pyr'_din-2 (IH) -one; I- [(2-acetyl-!,2,3,4-tetrahydroisoquinolin-6-Yl}methyl] 3-ch!oro-4- [ (2,4-dif!uorobenzyl)oxy]pyridin-2 (IH) -one; 3-chloro-4- [(2,4-dif!uorobenzyl)oxy]-l- [(2-glycoloylI, 2,3,4-tetrahydroisoquinolin6-yl) methyl] pyridin2 (IH) -one ; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l-{ [2- (2-hydroxy-2methylpropanoy!) - 1,2,3,4tetrahydroisoquinolin6- yl]methyl}pyridin-2 !H)-one; 3-chloro-4-[(2 4-difluorobenzyl)oxy]-l-{ [2- (Nmethy]glycyl)-l,2,3 4-tetrahydroisoquinolin-6yl] methyl}pyridin-2 !H) -one; 3-chloro-4- [(2 4-difluorobenzyl)oxy] -i-{ [2- (3hydroxypropanoyl) - 1,2,3,4tetrahydroisoquinolin6- yl ] methyl }pyridin-2 (IH) -one ; 3-chloro-4-[(2 4-difluorobenzyl)oxy]-l-{ [2- (3-hydroxy-3methylbutanoyl) -i, 2,3,4-tetrahydroisoquinolin-6yl] methyl}pyridin-2 (IH) -one ; 6- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl ] methyl } - 3,4 - dihydroisoquinoline-2 (IH) - carboxamide ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- { [2- (methylsul fonyl ) - I, 2,3,4 - t et rahydroisoquinol in6 - yl ] me t hyl } pyr i din2 ( 1 H) - one ; 3 -chloro-4 - [ (2,4 - di f luorobenzyl ) oxy] - 1 - ( i, 2,3,4 - tet rahydroi soquinol in5 -ylmethyl ) pyridin2 (IH) -one ; I- [ (2-acetyl-l, 2,3,4-tetrahydroisoquinolin-5-yl) methyl] 3-chloro-4- [ (2,4-difluorobenzy!) oxy] pyridin-2 (IH) -one ; 3-chloro-4- [(2,4-difluorobenzyl)oxy] -i- [ (2-glycoloyl1,2,3,4-tetrahydroisoquinolin-5-yl) methyl] pyridin-2 (IH) -one ; methylpropanoyl ) - 1 0 2,3,4 - t et rahydroisocfuinol in5 - yl] methyl }pyridin2 (IH) -one ; 3-chloro-4- [(2,4-difiuorobenzyl)oxy]-l-{ [2- (Nmethylglycyl) - 1,2,3,4 -cecrahydroisoquinolin5- yl]methyl}pyrid!n-2 (!H) -one; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -i-{ [2- (3hydroxypropanoyl)-! 2,3,4-tetrahydroisoquinolin-5yl]methyl}pyridin-2 !H)-one; 3-chloro-4- [ (2 4-difluorobenzyl)oxy] -i-{ [2- (3-hydroxy-3methylbutanoy!)-l,2 3,4-tetrahydroisoquinolin-5y!] methyl }pyridin-2 iH)-one; 5- { [3-ch!oro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl } -3,4-dihydrolsoquinoline-2 (IH) -carboxamide; 3-chloro-4- [ (2,4-difluorobenzy!)oxy]-l-{ [2- (methylsu!fonyl) - 1,2,3,4 - te:rahydroisoquino!in5- y! ] methyl }pyridin2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -i- (2,3-dihydro-IHbenzimidazol-5-ylmethyl) pyridin-2 (!H) -one; i- [(l-acetyl-2,3-dihydro-iH-benzimidazol-S-yl)methyl]-3chioro-4- [ (2,4-difluorobenzYl) oxy] pyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- [ (l-glycoloyl-2,3dihydroiH-benzimidazol ~ 5-yl) methyl] pyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -i- { [I- (2-hydroxy-2me thylpropanoyl ) -2,3 -dihydroIH-benz imidazol - 5 - yl ] me thyl ) pyri din2 (IH) ~ one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- { [i- (Nmethylglycyl ) -2,3dihydro-iH-benzimidazo1-5-yl ] methyl } pyridin2 (IH) -one ; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l-( [i- (3hydroxypropanoyl ) - 2,3 - dihydro1Hbenz imida zol - 5 - y!] methyl }pyridin-2 (IH} -one; 3-chloro-4- [ (2,4 -difluorobenzyl) oxy] -i- { [i- (3 -hydrexy3 methy!butanoyl) -2,3-dihydro- !H-benzlmidazol5- yl] methyl }pyridin2 (ill) -one ; 5-{ [3-ch!oro-4- [(2,4-difluorobenzyl)oxy]-2-oxopyridin- l(2H)-yl]methyl}-2,3-dihydro-!H-benzimidazo!e-l-carboxamide; 3-chloro-4- [(2,4-dif!uorobenzy!)oxy]-l-{ [l- (methylsu!fonyl)-2,3°dihydro-!H-benzimidazol-5yl] methyl }pyridin-2 (IH) -one ; !- [ (3-acetyl2,3 -dihydroIH-benzimidazol - 5-yl) methyl} - 3 - chloro-4- [ (2,4-difluorobenzyl)oxy]pyridin-2 (iH)-one; 3-chloro-l- [(l,3-diacetyl-2,3-dihydro-IH-benzimidazol-5yl) methyl] -4- [ (2,4-difluorobenzyl) oxy] pyridin-2 (IH) -one; i- [ (3-acetyl-l-glycoloyl-2,3-dihydro-iH-benzimidazol-5yl) methyl] -3-ch!oro-4- [ (2,4-difluorobenzyl)oxy] pyridin-2 (IH) - one ; i- { [3-acetylI- (2-hydroxy2-methylpropanoyl ) -2,3-dihydroIH-benzimidazol-5-yl]methy1}-3-chloro-4- [(2,4difluorobenzyl) oxy] pyridin-2 (IH) -one; i- { [3-acetyl-l- (iV-methylglycyl } -2,3-dihydro-IH- benzimidazol-5-yl] methyl }-3-chloro-4- [ (2,4difluorobenzyl) oxy] pyridin-2 (IH) -one; i- { [3 -acetyl -i- (3-hydroxypropanoyl) -2,3 -dihydroIHbenzimidazol-5-yl] methyl}-3-chloro-4- [ (2,4di f luorobenzyl ) oxy] pyridin2 (IH) - one ; 1 - { [ 3 - ace tyl - 1 - ( 3 - hydroxy3 - me thylbut anoyl ) - 2,3 - dihydroiH-benzimidazol-5-yl] methyl } -3-chloro-4- [ (2,4di f i uorobenzyl ) oxy] pyridin2 (IH) - one ; 3-acetyl-5- { [3-chloro-4 - [ (2,4 -difluorobenzyl)oxy] -2oxopyridin1 (2H) -yl ] methyl } -2,3-dihydroIH-benzimidazole-l- carboxamide; 1 o { [3-acetyl-i- (methylsulfonyl) -2,3-dihydro-IHbenzimidazol5-yl] methyl }- 3-chloro-4 - [ (2,4difluorobenzyl) oxy] pyridin-2 (IH) -one ; 3-chloro-4- [(2,4-difiuorobenzy!)oxy]-l- [(3-glyco!oyi-2,3 dihydro- !H-benzimida:ol-5-vl) me,by] ] p'?,ridin-2 (IH) -one; I- [(l-acetyl-3-clycoloy!-2,3-dihydro-lH-benzim'-dazol-5- yl)me=hy!] -3-ch!oro-4- [(2,4-difluorobenzvi)oxy]pyriizn-2 (!H) one ; 3-chloro-4- [(2,4-dzf!uorobenzy!)oxy]-l- [(i,3-dig!yccioy!- 2,3-dihydro-iH-benzimzdazol-5-y!)methy1]pyridin-2 (IH)-one; 3-chloro-4- [(2,4-difluorobenzyl)oxy] -!-{ [3-glycoioyl-l- (2-hydroxy-2-methylpropanoyl) -2,3 -dihydro-lH-benzimidazol-5yl ] methyl }pyridin-2 (IH) -one; 3-ch!oro-4- [(2,4-difluorobenzyl)oxy] -i-{ [3-glycoloyl-l- (N-methylglycyl) -2,3-dihydroIH-benzimidazo]- 5yl ] methyl }pyridin-2 (IH) -one ; 3-chloro~4- [ (2,4-difluoroben=yl)oxy] -i-{ [3-glycoloyl-!- (3-hydroxypropanoyl) -2,3-dihydroiH-benzimidazol5- yl] methyl }pyridin-2 (IH) -one; 3-chlcro-4- [ (2,4-difluorobenzyl) oxy] - I- { [3-glycoloy!-l- (3-hydroxy-3-methylbutanoyl) - 2,3 - dihydroIH-benzimidazol5- yl] methyl }pyridin-2 (]H) -one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl } -3-glycoloyl-2,3-dihydroIH-benzimidazole-lcarboxamide ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- { [3-glycoloyli- (methylsulfonyl) -2,3-dihydroiH-benzimidazol-5yl ] methyl }pyridin~2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - i- { [3- (2-hydroxy-2me thylpropanoyl ) - 2,3 - dihydro1 Hbenz imida zol - 5 - yl ] methyl } pyridin2 (IH) -one; i- { [l-acetyl3- (2-hydroxy-2-methylpropanoyl) -2,3-dihydroIH-benzimidazol-5-yl] methyl] ~3-chloro-4- [ (2,4difluorobenzyl) oxy] pyridin-2 (1H) -one ; (2-hydroxy-2-methylpropanoy!) -2,3-dihydroiH-benzimidazc! - 5yl] methyl}pyridin-2 (!H) -one; i- { [I, 3-bis (2-hydroxy-2-methyipropanoyl) -2,3-dihvdro- !H- benzimidazol-5-yl]methy!}-3-chloro-4- [(2,4difluorobenzyl) oxy] pyridin-2 (IH) -one ; 3-chloro-4- [(2,4-dif!uorobenzyl)oxy] -!-{ [3- (2~h.vdroxy-2methylpropanoyl) - i- (N-methylglycyl) - 2,3-dihydroIHbenzimidazol-5-yl] methyl }pyridin-2 (IH) -one; 3-chloro4- [ (2,4-dif!uorobenzyl) oxy] - i- { [3- (2-hydroxy2- methy!propanoyl) - i- (3-hydroxypropanoyl) -2,3-dihydroIHbenzimidazol-5-yl] methyl }pyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - I- { [1- (3-hydroxy3- methylbutanoyl ) - 3 - (2 -hydroxy2 - methylpropanoyl ) - 2,3 -dihydro- iH-benzimidazol-5-yl]methyl}pyridin-2 (IH) -one; 5- { [3-chloro-4- [ (2,4-difluorobenzy]) oxy] -2-oxopyridin1 (2H) -yl] methy! } -3- (2-hydroxy-2-methylpropanoyl) -2,3-dihydroIHbenzimidazol e ~ 1 - carboxamide ; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l-{ [3- (2-hydroxy-2- methylpropanoyl) ~i- (methylsulfony!) -2,3-dihydro-iHbenzimidazol - 5 -yl ] methyl } pyridin2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- { [3- (Nmethylglycyl ) - 2,3 -dihydroIHbenzimida zol - 5 -yl ] methyl } pyridin2(IH)-one; i- { [l-ace yl-3- (N-methylglycyl) -2,3-dihydro-IHbenzimidazol-5-yl]methyl}-3-chloro-4- [ (2,4difluorobenzyl) oxy] pyridin-2 (IH) -one; 3~chloro-4- [ (2,4-difluorobenzyl) oxy] -i° { [l-glycoloyl-3- (N-methylglycyl) -2,3-dihydroIH-benzimidazol-5- yl]methy1}pyridin-2 (IH) -one; 3-chloro-4- [ (2,4 ~difluorobenzyl) oxy] -i- { [l- (2-hydroxy-2methylpropanoyl ) -3 - (N-methylglycyl) -2,3 -dihydroIHbenzimidazol-S-y!] methyl }pyridin-2 (ill) -one ; 1-{ [l,3-bis(N-methylgiycyl)-2,3-iihydro-iH-benzimiiazol3-y!]mezhyl}-3-chloro-4- [{2,4-dif!uorobenzy:}oxy]pyr!/in2 (iH)-one; 3-chioro-4- [(2,4-difluorcbenzyl)cxy]-l-{ [i- {3hydroxypropanoyi } -3- (N-me[hy! g! ycy i } - 3-dihydroiHbenzimidazol-5-yi]methyl}pyrid!n-2 (iH)-one; 3-chloro-4- [ (2,4-dif!uorobenzyl)oxy]-!-{ [I- (3-hvdroxy-3methylbuEanoyl) -3- (N-methylglycyl) -2,3-dihydroIH- benzimidazoi-5-yl]methyl }pyridin-2 iH)-one; 5-{ [3-ch!oro-4- [ (2,4-difluorobenzy!)oxy] -2-oxopyridinI (2H)-yl]methyl)-3- (N-methylglycyl)-2,3~dihydro-iHbenz imida zol e - 1 - carboxami de ; 3-ch!oro-4-[(2,4-difluorobenzyl)oxy]-l-{ [3- (N- methylglycyl)-l-(methylsulfonyl)-2,3-dihydro-IH-benzimida=ol5-yl] methyl }pyridin-2 (IH) -one ; 3-chlorc-4- [ (2,4-difluorobenzyl)oxy]-l~{ [3- (3hydroxypropanoyl) - 2,3 -dihydroiH-benzimidazol - 5yl ] methyl }pyridin-2 (IH) -one ; 1 - { [iacetyl3- (3 -hydroxypropanoyl) - 2,3-dihydroIHbenzimidazol-5-yl] methyl }-3-chloro-4- [ (2,4difluorobenzyl) oxy] pyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -i-{ [l-glycoloyl-3~ ( 3 - hydroxypropanoyl ) - 2,3 - di hydro - 1 Hben z i mi da z o i - 5 - yl] methyl}pyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - I- { [I- (2-hydroxy-2methylpropanoyl ) -3 - (3 - hydroxypropanoyl) -2,3 -dihydroIHbenzimidazol-5-yl] methyl }pyridin-2 (IH) -one; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l-{ [3- (3- hydroxypropanoyl) -I- (N-methylglycyl) - 2,3-dihydroIHbenzimidazol-5-yl] methyl }pyridin2 (IH) -one ; i- { [ I, 3-bis (3-hydroxypropanoyl) -2,3-dihydroIHbenzimidazol-5-yl]methyl}-3-chloro-4- [(2,4dlfluorobenzyl) oxy] pyridin-2 (IH) -one; 3-chloro-4- [(2,4-difluorobenzyl)oxy.]-l-{ [!- (3-hydroxv-3methylbutanoyl) - 3- (3-hydrox.vpropanoy!) - 2,3-dihydrc- !Y- benzimidazol5-y! ] methyl }pyridin2 (IH) -one; 5-{ [3-chloro-4- [ (2,4-difluorobenz},l)oxy] -2-oxopvridinI (2H) -yl] methy! }-3- (3-hydroxypropanoyl) -2,3-dihydro-!Hbenzimidazolel-carboxamide ; 3 -chloro-4- [ (2,4-difluorobenzvl) oxy] - I- { [3- (3- hydroxypropanoyl) -I- (methylsulfonyl) -2,3-dihydro-iHbenzimidazol-5-yl] methyl }pyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - I- { [3- (3-hydroxy-3 methylbutanoy!) - 2,3-dinydroiH-benzimidazol5- yl]methyl}pyridin-2 (iH)-one; I-{ [l-acetyl-3- (3-hydroxy-3-methylbutanoyl) -2,3-dihydro1H-benzimidazol-5-yl]methyl}-3-chloro-4- [ (2,4difluorobenzyl)oxy]pyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl)oxy]-l-{ [l-glycoloyl-3- (3-hydroxy3-methylbutanoyl) -2,3-dihydroiH-benzimidazol- yl]methyl}pyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - I- { [3-(3-hydroxy-3methylbutanoyl ) - 1 - (2 - hydroxy2 -methylpropanoyl ) - 2,3 -dihydroiH-benzimidazo1-5-yl] methyl }pyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -1- { [3- (3-hydroxy-3- methylbutanoyl) -I- (N-methylglycyl) -2,3-dihydroIHbenzimidazol - 5 -yl ] methyl }pyridin2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- { [3- (3-hydroxy-3methylbutanoyl ) -I - (methylsul fonyl ) -2,3 -dihydro1Hbenzimidazol-5-yl ] methyl )pyridin-2 (IH) ~one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl ] methyl } - 3- (3-hydroxy-3-methylbutanoyl) -2,3-dihydroIHbenz i mida zol e - 1 - carboxamide ; I- { [I, 3-bis (3-hydroxy-3-me hylbutanoy!) -2,3-dihydrc-:Hbenzimidazoi-5-yl]me%hy!}-3-ch!oro-4- [(2,4difluorobenzyl) oxy] pyridin-2 {IH) -one; 3-chloro-4- [(2,4-difluoroben:y!)oxy] -!-{ [3- (3-hydroxy-3- methylbucancyl) -i- (3-hydroxypropanoyl)-2,3-dihvdra-IHbenzimidazol5-yl] methyl }pyridin-2 (ill) -one ; 6-{ [3-chloro-4- [ (2,4-dif!uorobenzyl)oxy] -2-oxcpyridini (2H) -yl ] methyl } - 2,3-dihydroiH-benzimidazele- !-carboxamide ; 3-acetyl-6-{ [3-chloro-4- [(2,4-difluorobenzyl)ox v]-2- oxop_vrldini (2H) -yl] methyl }-2,3-dihydroiH-benzimidazolel- carboxamide ; 6-{ [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -2-o×opyridinI (2H} -yl] methyl} -3-glycoloyl-2,3-dihydro-iH-benzimidazole-lcarboxamide ; 6- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin- !(2H) -y!]methyl}-3- (2-hydroxy~2-methylpropanoyl) -2,3-dihydro- !H-benzimidazo!ei- carboxamide; 6-{ [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -2-oxopyridin1 (2H) -yl ] methyl } - 3- (N-methylglycyl) - 2,3-dihydroIH- benzimidazolel-carboxamide ; 6- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 ( 2 H) - yl ] me thyl } - 3 - ( 3 -hydroxypropanoyl ) - 2,3 - dihydro1 Hbenzimida zole - 1 - carboxamide ; 6- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin- 1 (2H) - yl ] methyl } - 3 - ( 3 - hydroxy3 - methylbut anoyl ) - 2,3 - dihydroIHbenzimida zole - 1 - carboxamide ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl ] methyl } - iH-benzimidazole-l, 3 (2H) -dicarboxamide ; 6- { [3-chloro-4 ~ [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl ) ~ 3- (methylsul fonyl) -2,3-dihydroIHbenzimida zole1 -carboxamide ; (methylsulfonyl) -2,3-dihydro- !H-ben=imida=el-5yl] methyl }pyridin-2 (IH} -one ; i-{ [l-acetyl-3- (methylsulfony!)-2,3-dihvdro-iHbenzimidazol-5-y!]methy!}-3-chloro-4- [(2,4- difluorobenzy!)oxy]pyridin-2 (IH) -one; 3-chloro-4 - [ (2,4-dif!uorobenzy!) oxy] - !- { [l-glyco!ovl-3 - (methylsul fony!) -2,3-dihydroiH-benzimidazol-5y!] methyl }pyridin-2 (!H)-one; 3-chloro-4- [(2,4-difluorobenzyl)oxy] -i-{ [I- (2-hydroxy-2- methy!propanoyi) - 3- (methylsulfonyl) -2,3 -dlhydroIHbenzimidazol-5-yl]methyl}pyridin-2 (!H) -one; 3-ch!oro-4- [ (2,4-difluorobenzyl)oxy] -!-{ [i- (Nmethylglycyl) - 3- (methylsulfonyl) -2,3-dihydro-IH-ben=imidazol5-yl] methyl }pyridin-2 {IH) -one; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l-{ [i- (3hydroxyprcpanoyl) - 3- (methylsul fonyl) -2,3-dihvdro- !Hbenz midazo!- 5-y!] methy! }pyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - i- { [I- (3 -hydroxy-3methy!butanoyl) - 3 - (methylsul fonyl) -2,3 -dihvdroIH- benzimidazo!- 5-yl ] methyl }pyridin-2 (IH) -one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl]-3- (methylsulfony!) -2,3-dihydro-iHbenzimidazolei-carboxamide ; i-{ [I, 3-bis (methylsul fonyl) -2,3-dihydroIH-benzimidazol- 5-yl ] methyl } - 3 -chloro-4 - [ (2,4 -di fluorobenzyl ) oxy] pyridin2 (IH)-one; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl)-l, 3-dihydro-2H-benzimidazol-2-one ; l-acetyl-5- ( [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2- oxopyridin1 (2H) -yl] methyl ]-i, 3-dihydro-2H-benzimidazol-2-one; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl]methyl}-l-glycoloyl-l,3-dihydro-2H-benzimidazol-2l(2H)-yl]methyl}-!- (2-hydroxy-2-methy!propanoy!)-!,--dihydre2H-benzimidazo!- 2-one; 5-{ [3-ch!oro-4- [(2,4-difluorobenzyl)oxy]-2-oxoc}'rzd'-n1 (2H) -yl] methyl } - i- (N-methylglycy! } - i, 3-dihydro2Hben=imzdazol2-one ; 5- { [3-chloro-4- [ (2,4-difluorobenzy!) oxy] -2-oxcpyr-dini (2H) -yl] methyl } - 1 - (3-hydroxypropanoyl) - I, 3 -dihydro-2H- benzimidazoi2-one ; 5-{ [3-chloro-4- [ (2,4-difluorobenzyl}oxy] -2-oxopyridin1 (2H) -yl] methyl } -i - (3-hydroxy-3-methylbutanoy!) -i, 3-dihydro2H-benzzmidazol2-one ; 5- { [3-chloro-4- [ (2,4-dif!uorobenzyl) oxy] -2-oxopyridin- 1 (2H)-yl]methyl}-2-oxo-2,3-dihydro-iH-benzimidazole-!- carboxami de ; 5-{ [3-chloro-4- [ (2,4-difluorobenzyl)oxy]-2-oxopyridin1 (2H)-yl]methyl}-l- (methylsulfony!)-l,3-dihydro-2Hbenzimidazol2-one ; l-acetyl-6-{ [3-chloro-4- [(2,4-difluorobenzyl}ox¥]-2oxopyridin1 (2H) -yl] methyl } - i, 3-dihydro-2H-benzimidazol-2-one i, 3-diacetyl-5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2oxopyridin1 (2H) -yl ] methyl } - i, 3 -dihydro2H-benzimidazol - 2 -one ; 3-acetyl5- { [3-chloro~4- [ (2,4-difluorobenzyl) oxy] -2- oxopyridin1 (2H) -yl] methyl } -i -glycoloyl - I, 3 -dihydro-2Hbenzimidazol - 2 -one ; 3-acetyl-5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2oxopyridin1 (2H) ° yl ] methyl } - 1 - (2 - hydroxy2 - methylpropanoyl ) - i, 3-dihydro-2H-benzimidazol-2-one; 3 -acetyl5- { [3 -chloro-4- [ (2,4 -difluorobenzyl) oxy] -2oxopyridin1 (2H) -yl] methyl } -i- (N-methylglycyl) - i, 3-dihydro-2Hben:imidazol-2-one ; oxopyridin1 (2H) -yl] methy! } - !- (3-hydroxypropanoyl) - i, 3dihydro-2H-benzimidazol-2-one ; 3-acetyl-5-{ [3-chloro-4- [(2,4-difluorobenzy!)exy]-2" oxopyridin1 (2H) -yl ] methyl } - i- (3-hydroxy3-menhylbutanoy!) - 1,3-dihydro-2H-benzimidaz°l2-one ; 3-acety--5-{ [3-chloro-4- ['(2,4-dif!uorobenzy!)oxy] -2oxopyridin1 (2H) -yl] methyl } - 2-oxo-2,3-dihydroIHbenzimidazoleI- carboxamide ; 3-acety!-5-{ [3-chloro-4- [(2,4-dif!uorobenzy!)cxy] -2oxopyridin1 (2H) -yl ] methyl } - i- (methylsul fonyl) - !, 3-d!hydro2Hbenzimidazol - 2 -one ; 6- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H)-yl]methyl}-l-glycoloyl-I 3-dihydro-2H-benzimidazol-2one ; l-acetyl-5-{ [3-chloro-4- [ 2,4-difluorobenzyl)oxy]-2oxopyridin1 (2H) -yl ] methy! } - 3-glycoloyl1,3-dihydro2Hbenz imi da zo I - 2 - one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl ] methyl} - i, 3-diglycoloyl - i, 3 -dihydro-2H-benzimidazol2 - one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl ] methyl } - 3 -glycoloyl - 1 - ( 2 -hydroxy2 °methylpropanoyl ) - i, 3 -dihydro2H-benzimidazol - 2 -one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl } -3 -glycoloyl - 1 - (N-methylglycyl) - l, 3 - dihydro2H-benzimidazol-2-one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyls-3-glycoloylI- (3-hydroxypropanoyl) - i, 3dihydro2H-benzimidazol - 2 - one ; 5-{ [3-chloro-4- [(2,4-difluorobenzyl)oxy]-2-oxopyridin1 (2H) -yl] methyl}-3-glycoloy!-l- (3-hydroxy-3-methylbutanoyl) - I, 3-dihydro-2H-benzimidazoi2-one ; 5- { [3-chloro-4- [ (2,4-dl f!uoroben--y-) oxy] - 2 -cxopyr: din- ! H)-yl]methyl} 3-$iycoloyl-2-oxe-2 -dihvdrow_ benz-midazole-!-carboxamzde ; _=-{ [3-ch!oro-4- [(2,-.-di[luoreben--y oxv] -2-oxo ....... i (2H) -yl] methyl } -3-g!ycoloyii- (methylsu!fony!) - !, 3-dlhydro2H-benzimidazol2-one ; 6-{ [3-chloro-4- [(2,4-dif!uorobenzyl)oxy]-2-oxopyridin1 (2H) -yl ] methyl } - i- (2 -hydroxy2-methy!propanoyl) - i, 3-dihydro- 2H-benzimidazol - 2 -one ; l-acety!-5-{ [3~ch!oro-4- [ (2,4-dif!uoroben:¥1)oxy] -2oxopyrldin1 (2H) -yi ] methyl } - 3 - (2 -hydroxy2-me<hylpropanoyl) - I, 3-dihydro-2H-benzimidazol-2-one; 5-{ [3-ch!oro-4- [ (2,4-difluorobenzyl)oxy]-2-oxopyridin- l(2;4)-yl]methyl}-!-glyco!oyl-3-(2-hydroxy-2-methylpropanoyl)- !, 3-dihydro2H-benzimidazol-2-one ; 5-{ [3-chloro-4- [(2,4-difluoroben--yl)oxy]-2-oxopyridin1 (2H) -yl ] methyl ] - 1,3-bis (2-hydroxy2-methylpropanoyl) - 1,3dihydro-2H-benzimidazoi-2-one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridinI (2 H) - yl ] me t hyl } - 3 - ( 2 - hydroxy2 - met hyl propanoyl ) - 1 - (Nmethylglycyl ) - i, 3 - dihydro2Hbenzimi da zol - 2 - one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl ] methyl } -3 - (2-hydroxy-2-methylpropanoyl ) -1- (3 - hydroxypropanoyl ) - i, 3 - dihydro2H-benzimidazol - 2 - one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl}- I- (3-hydroxy-3-methylbutanoyl) -3- (2-hydroxy2 -methylpropanoyl ) -i, 3 - dihydro2H-benzimidazo1-2 -one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin- 1 (2H) -yl] methyl } - 3- (2-hydroxy-2-methylpropanoyl) -2-oxo-2,3dihydro - IHbenzimidazol e - 1 - carboxamide ; 1 (2H) -yl] methyl } -3- (2-hydroxy-2-me -hylpropanoyl) - l- (methylsulfonyl) - I, 3-dihydro-2H-benzlmidazo!-2-one ; 6- { [3-chloro-4- [ (2,4-difluorobenzvl) oxy] -2-oxopyridin- ! (2H) -yl] methyl } -i- (N-methylglycyl) - I, 3-dlhydro-2H- benzimidazol2-one ; !-acetyl-5-([3-chloro-4- [(2,4-difluorobenzyl)exy]-2oxopyridin- ! (2H) -yl ] methyl } - 3- (N-methylglycyl) - i, 3-dihydrobenzimidazol-2-one ; 5-I [3-chloro-4- [ (2 4-difluorobenzyl)oxy]-2-oxopyridin- 1 (2H) -y! ] methyl } -! -glycoloyl -3 - (N-methylglycyl) -I, 3 -dihydro2H-benzimidazol-2-one ; 5-{ [3-chloro-4- [ (2 4-difluorobenzyl)oxy]-2-oxopyridin1 (2H) -yl] methyl }- i- (2-hydroxy-2-methylpropanoyl) -3- (Nmethylglycyl) - i, 3-dihydro-2H-benzimidazol2-one ; 5-{ [3-chloro-4- [(2 4-difluorobenzyl)oxy]-2-oxopyridin- ! (2H) -yl] methyl }-I, 3-bis (N-methylglycyl) -I, 3-dihydro-2Hbenzimidazol - 2 - one ; 5-{ [3-chloro-4- [(2 4-difluorobenzyl)oxy]-2-oxopyridin1 (2H) -yl ] methy! } - I- (3-hydroxypropanoyl) - 3- (N-methylglycyl) - i, 3-dihydro-2H-benzimidazol-2-one; 5-{ [3-chloro-4-[(2 4-difluorobenzyl)oxy]-2-oxopyridin1 (2H) -yl] methyl }- I- (3-hydroxy-3-methylbutanoyl) -3- (Nmethylglycyl ) - i, 3 - dihydro2H-benzimida zol -2 -one ; 5-{ [3-chloro-4- [(2 4-difluorobenzyl)oxy]-2°oxopyridin- 1 (2H) -yl]methyl}-3- (N-methylglycyl) -2-oxo-2,3-dihydro-iHbenzimidazole1 -carboxamide ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl }-3- (N-methylglycyl) -i- (methylsulfonyl) -i, 3di hydro2Hbenz imida zol - 2 - one ; 6-{ [3-chloro-4- [ (2 4-difluorobenzyl)oxy]-2-oxopyridin1 (2H) -yl] methyl }-I- (3-hydroxypropanoyl) - I, 3-dihydro-2Hbenzimidazol-2-one ; oxopyridin-I (2H) -yl] methyl } -3- (3-hydrexl ropancyl) - L, 3dihydro-2H-bentimidazol-2-one ; 5-{ [3-chloro-4- [(2 4-difiuorobenzyl)oxv]-2-oxo yrldin1 (2H)-y!]methyl}-i-g!yco!oy!-3-(3-hydrox}qpropaney!) -I, 3dihydro-2H-benzim=dazol2-one ; 3-{ [3-ch!oro-4- [(2 4-dlf!uorobenzyl)oxy]-2-oxop.vridinI(2H) -yi]methyl}-!-(2-hydroxy-2-methylpropanoyl)-3-(3hydroxypropanoyl ) - "_,3-dihydro-2H-benzimidazo!-2-one; 5-{ [3-chloro-4-[(2,4-difluorobenzyl}oxy]-2-oxopyridin1 (2H) -y!]methyl}-3-(3-hydroxypropanoyl)-l-(N-methy!91ycyl)- I, 3-dihydro-2H-benz imidazol-2-one; 5-{ [3-chloro-4- [(2 4-difluorobenzyl)oxy]-2-oxopyridinI (2H) -yl] methyl }-I, 3-his (3-hydroxypropanoyl) -!, 3-dihydro-2H- benzimidazol-2-one ; 5-{ [3-chloro-4-[(2 4-difluorobenzyl)oxy]-2-oxopyridin1 (2H) -yl] methyl } -i- (3-hydroxy-3-methylbutanoyl) - 3- (3hydroxypropanoyl) - 1,3-dihydro-2H-benzimidazol2-one ; 5-{ [3-chloro-4- [ (2 4-dif!uorobenzyl)oxy]-2-oxopyridin- i (2H) -yl ] methyl } - 3- (3-hydroxypropanoyl) -2-oxo-2,3-dihydroIHbenzimidazole1 -carboxami de ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 ( 2 H) - yl ] met hyl } - 3 - (3 - hydroxypropanoyl ) - 1 - (me thyl sul fonyl ) - i, 3 - dihydro2H-benzimidazol - 2 -one ; 6-{ [3-chloro-4- [(2 4-difluorobenzyl)oxy]-2-oxopyridin1 (2H) -yl] methyl }-i- (3-hydroxy-3-methylbutanoyl) - I, 3-dihydro2 Hbenz imida zol - 2 - one ; l-acetyl-5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2oxopyridin1 (2H) -yl ] methyl } - 3 - ( 3 -hydroxy3 -methylbutanoyl ) - I, 3-dihydro-2H-benzimidazol-2-one; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl ] methyl } - 1 -glycoloyl - 3 - ( 3 - hydroxy3 -methylbut anoyl ) - I, 3 - dihydro2Hbenzimidazo! - 2 -one ; - { [3 - chloro4 - [ (2,4 -dl f!uorobenzy! ) oxy] - 2 -oxopvridin~ 1 (2H) -yl] methyl }-3- (3-hydroxy-3-methylbu anoyl) -I- (2-hydrcxy2-me[hylpropanoyl) -i, 3-dihydro-2H-benzimidazol-2-one; 5-{ [3-chloro-4- [ (2 4-difluorobenzyl)oxy] -2-oxcpyridin- !(2H)-yl]methyl}-3- (3-hydroxy-3-methylbutanoyl)-!-(Nmethylglycyl) -i, 3-dihydro2H-benzimidazol-2-one; 5-{ [3-chloro-4- [ (2 4-difluorobenzyl)oxy]-2-oxopyrldin- ! (2H) -yl] methyl } -3- (3-hydroxy-3-methylbutanoyl) - I- ( - hydroxyp_ropanoyl) - l, 3 -dihydro2H-benzimidazol2-one ; 5-{ [3-chloro-4- [ (2 4-difiuorobenzyl)oxy]-2-oxopyridin- ! (2;{) -yl] methyl } - I, 3-bis (3-hydroxy-3-methylbutanoyl) -i, 3d i hydro - 2 Hben zimi da z o i - 2 - one ; 5-{ [3-chloro-4- [ (2 4-difluorobenzy!)oxy]-2-oxopyridin1 ( 2 H) - yl ] me t hyl } - 3 - ( 3 - hydroxy3 - me t hyl but anoy i ) - 2 - oxo - 2,3 - dihydroIHbenzimidazo! e1 - carboxamide ; 5-{ [3-chloro-4- [(2 4-dif!uorobenzyl)oxy]-2-oxopyridin1 (2H) -yl] methy! } - 3- (3-hydroxy3-methylbutanoyl) -l- (met hyl sul fonyl ) - 1,3 - dihydro2 Hbenzimidazol - 2-one ; 6-{ [3-chloro-4- [(2 4-difluorobenzyl)oxy] -2-oxopyridin1 ( 2 H) -yl ] methyl } - 2 - oxo - 2,3 - dihydroIHbenzimidazole - 1 - carboxamide ; 3-acetyl-6- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2oxopyridin1 (2H) -yl ] methyl } - 2 -oxo2,3 -dihydroIHbenzimida zol e - 1 - carboxamide ; 6- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl} -3-glycoloyl-2-oxo~2,3-dihydroIHbenzimidazol e - 1 - carboxamide ; 6- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridini (2H) -yl] methyl} -3- (2 -hydroxy-2-methylpropanoyl) -2-oxo-2,3dihydroIHbenzimida zol e ~ 1 - carboxamide ; i (2H) -yl] methyl } -3- (N-methylg!ycy!) -2-ox0-2,3-dihydro-iA'- ben"_ imi da zo! e - i - c arboxami de ; 6-{ -ch-oro--.- .i [(2, .-Qi luorobenzyl)oxy] " = - 2-oxo:vr din__ ! ([H) -yl] methyl } -3- (3-hydroxypropanoyl) -2-oho2,3-dihydrcIH- benzimida zo! e- ! - carboxamide ; 6-{ [3-ch!oro-4- [(2,4-difluorcbenzyl)oxy]-2-oxoTvrl/in- !(2H)-yl]methy!}-3- (3-hydroxy-3-methyibutanoy!} -2-oxo-2,_:- dihydro-!H-benzimidazolei-carboxamide ; 5-{ [3-chloro-4-[ (2,4-difluorobenzyl)oxy]-2-oxopyr'-din- 1 (2H)-yl]methy!}-2-oxo-iH-benzimidazole-l,3 (2H) -dicarboxamlde; 6-[ [3-ch!oro-4- [ (2,4-difluoroben=yl)oxy] -2-oxopyridinI (2H) -yl] methyl } -3- (methylsul fonyl) - 2-oxo2,3-dihydroIHbenzimidazole-!-carboxamide ; 6-{ [3-chloro-4- [ (2,4-difluorobenzyl)oxy]-2-oxopyridin- ! (2H) -vl ] methyl } - I- (methylsu!fonyl) - 1,3-dihydro2Hbenzimidazol-2-one ; l-acetyl-5-{ [3-ch!oro-4- [ (2,4-difluoroben_-yl)oxy] -2oxopyridinI (2H) -yl] methyl } -3- (methylsulfonyl) - !, 3-dihydro-2Hbenzimidazol-2-one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] - 2-oxopyridini (2HI -yl] methyl}-l-glycoloyl-3- (methylsulfonyl) -I, 3-dihydro2H-benzimidazo1-2-one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl ] methyl } - 1 - ( 2 - hydroxy2 -methylpropanoyl ) - 3 - (methylsulfonyl) -i, 3-dihydro-2H-benzimidazol-2-one; 5-{ [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl } -i- (N-methylglycyl) -3- (methylsulfonyl) - I, 3dihydro2Hbenzimidazol - 2 -one ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin- 1 ( 2 H) - yl ] methyl ) - 1 - ( 3 - hydroxypropanoyl ) - 3 - (me t hyl su! fonyl ) - i, 3-dihydro-2H-benzim dazol_ 2-one ; 1 (2 H) -y!] methyl } - ! - ( 3 -hydroxy-3 -met hy!but anoyl ) -3 - (methylsulfony!) -l, 3-dihydro-2H-benzimidazol-2-one; 5-{ [3-chloro-4- [(2,4-difluorobenzy!)oxy]-2-°x°pyridin1 (2H) -y!] methy! }-3- (methylsulfonyl) -2-oxo-2,3-dihydro-!H- benzimidazole1 - carboxamide ; 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] - 2-oxopyridini (2H) -yl] methyl } -i, 3-bis (methylsulfonyl) - i, 3-dihydro2Hbenzimidazol-2-one ; 3-benzyl-4 -hydroxyi- (2-phenylethyl) pyridin2 (IH) - one ; l-benzyl-4 -hydroxy-2-oxo1,2-dihydropyridine3 - carbaldehyde ; 1 - benzy1-4 - chloro2 -oxo1,2 - dihydropyridine - 3 - carba!dehyde ; methyl 5-chloro-l- (4-chlorobenzyl)-6-oxo-l,6- dihydropyridine3- carboxyl ate ; 5-bromoi- (2-chloro-6fiuorobenzyl) -3-methylpyridin2 (iH)-one; 3-bromo-l- (2,6-dichlorophenyl) -4- [ (4fiuorophenyl) ethynyl] -6-methylpyridin-2 (IH) -one ; 3-bromo-l- (2,6-dichlorophenyl) -4- [ (4f luorophenyl ) ethynyl ] - 6 -methylpyridin2 (IH) -one ; methyl 3-chloro-4- [4- [ (2,4-difluorobenzyl)oxy]-6-methyl2 -oxopyridin1 (2H) -yl ] benzoate ; 4- [ (2,4-difluorobenzyl) oxy] -I- (3-fluorobenzyl) -2-oxo-I, 2- dihydropyridine-3-carbonitrile ; 4- [ (2,4-difluorobenzyl) oxy] -6- (hydroxymethyl) -i- (2,4,6tri f luorophenyl ) pyridin-2 (IH) -one ; 4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [2- (tri f luoromethyl ) phenyl] pyridin2 (IH) -one ; 3- [4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl] benzaldehyde ; 4-ylphenyl) -6-meuhy!pyridin-2 (IH] -one; 4- [ (2,4-d'if!uorobenzy!) oxy] - !- [2,6-iifluoro-4- (4me=hylpipera=ini-yi) pheny!] - 6-methy!pyr-d -2 { : = 3- [3-bromo-4- [(2,4-dif!uorobenzy!)oxy]-6-me=h.v!-2- oxomvridin-i_. (2H) -- i" ]ben:oic acid; 4- [(2,4-difluorobenzyi)oxy]-l- [4- (dimeth?'!amino! -2, 4d! f luoropheny!] - 6-methy!pyridin-2 (!H) -one; 4- [(2,4-difluorobenzy!)oxy]-!-{2,6-dif!uoro-4- [(2hvdroxye hyl) (methy!) amino] phenyl } -6-methylpyridin2 (!H) -one ; methyl 3- [3-bromo-4- [(2,4-difluorobenzyl)oxy] -6-methy!-2cxopyridzn- ! (2H) -y!] benzoate ; 3- [4- [ (2,4-difluorobenzyl) oxy] - 6-methyl2-oxopyridin- ! (2H) -yl] -4-methylbe zoic acid; 4- [(2,4-difluorobenzy!)oxy]-l-(2,6-difluoropheny!)-6- (hydroxymethyl) pyridin-2 (IH) -one ; 3-bromo-l-{ [S- (chloromethyl)pyrazin-2-yl]me=hyl}-4- [ (2,4difluorobenzyl) oxy] - 6-methylpyridin2 (IH) -one ; !- [2-chioro-5-(hydroxymethyl)phenyl]-4- [(2,4di fluorobenzy!) oxy] - 6-methy!pyridin-2 (IH) -one ; 4- [ (2, 4-difluorobenzyl) oxy] -!- (2,6-dif!uoro-4hydroxyphenyl ) - 6 -methylpyridin2 (IH) - one ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -I- [4- (hydroxymethyl) 2 -methoxyphenyl ] - 6 -methylpyridin2 (IH) - one ; methyl 3- [3-bromo-4 - [ (2,4 -difluorobenzyl) oxy] -6-methyl-2- oxopyridin-I (2H) -yl] -4-methylbenzoate; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [ 3- [ (4methylpiperazin-l-yl) carbonyl] phenyl }pyridin-2 (IH) -one ; 3- [3-bromo-4- [(2,4 ~difluorobenzyl)oxy]-6-methyl-2oxopyridin-i (2H) -yl] -N- [2- (dimethylamino) ethyl] benzamide; 3- [3-bromo-4- [ (2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-I (2H) -yl] -N- (2-methoxyethyl) benzamide ; oxopyridin1 (2H) -y-I -N- [2- (dimeth}'!amino) ethyl -Nmethylbenzamide ; 3- [3-bromo-4-[(2,4-difluorobenzyl)ox}']-6-methy!-2oxopyl-ldin-1 (2H) -v!] -N- (2-hydroxyethyl) -N-methylbenzamiie; 3- [3-bromo-4- [(2,4-dif -uorobenzyl)oxy]-6-methyl-2oxopyridin- ! (2H) -yl] -N- (2-methoxyethyl) -N-methylbenzamide ; 4- [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin1 (2H) -yl] benzamide ; methyl 3- [3-chloro-4- [(2,4-difluorobenzyl)oxy]-6-me hyl- 2-oxopyridin-!(2H)-yl]-4-fluorobenzoate; 4- [4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)-yl] -3-methy!benzoic acid; i- (4-bromo-2-methylphenyl} -4- [ (2,4-difluorobenzyl) oxy] me-hy!pyridin2 (IH) -one ; !- [ (l-acetyliH-indol5-yl) methyl] -3-ch!oro-4- [ (2,4dif!uorobenzy!) oxy] pyridin-2 (IH) -one; 3-bromo-4- [ (2,4-dif!uorobenzyl) oxy] -6-methyl-l- [ (5methylpyrazin-2-y!) methyl] pyridin-2 (IH) -one; methyl 2- ({ [3-bromo~l- (2,6-difluorophenyl)-6-methyl-2- oxo-l, 2-dihydropyridin-4~yl] oxy}methyl) -3,5di f luorobenzyl carbama t e ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -i- { [5- ( hydroxymethyl ) pyrazin2 ~yl ] methyl } - 6 - methylpyri din2 (IH) - 4- { [3-bromo-4- [ (2,4 ~difluorobenzyl) oxy] -6-methyl-2- oxopyridin1 (2H) -yl] methyl } -N, Ndimethylbenzamide ; 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl ] -N- (2 - hydroxyethyl ) -4 -methylbenzamide ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- {4- [ (4met hylpiperazin1 -yl ) carbonyl ] benzyl } pyridin2 (IH) ~one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- (IHindol-5ylmethyl) pyridin-2 (IH) -one ; oxopyridini (2H) -y! ] -Nmenh.vlbenzamide ; 3- [3-bromo-4- [(2,4-difluorobenzyi)oxy]-6-methy!-=- oxopyridini (2H) -y!] benzamide; -chloro-4- [ (2,4-difluorobenzyl) oxy] - i- { [5- (hydroxymethy!) pyrazln-2-y!] methyl }-6-methylpvridin-2 3- [3-bromo-4- [ (2,4-difluoroben:yl) oxy] -6-methyloxopvridin1 (2H) -yi ] -N- (2-methoxvethy!) -4-methy!ben=amide 3- [3-bromo-4- [ (2,4-difluorobenzyl)oxy]-6-methy!-loxopyr!din-I (2H) -yl ] -N, 4-dimethy!benzamide; 3- [3-bromo-4- [ (2,4-dlfluorobenzy!) oxy] -6-methyl -2oxopyridin1 (2H) -y! ] -N, N, 4-trimechylbenzamide ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6 -methyl- !- [2 5- (morpho!in-4-ylcarbonyl) phenyl] pyridin-2 (IH) -one ; 3-bromo-4- [(2,4-difluoroben:yi)oxy]-l- [5- (l-hydroxv-l- methylethyl) -2-methylphenyl] -6-methylpyridin-2 (!H) -one; i- (2-bromobenzyl) -3- [ (2-bromobenzyl) oxy] pyridin-2 one ; I- (2-bromobenzyl) -3- [ (2-bromobenzy!) oxy] pyridin-2 one ; 3-bromoi- (4-methoxybenzyl) -4-phenoxypyridin2 (!H) 1 - benzyl - 2 - oxo - 4 - phenoxyI, 2 - dihydropyr i dine - 3 - carba!dehyde ; 3-Bromo-4- (2,4-difluoro-benzyloxy) -i- (3dimethyl aminome t hyl - benzyl ) - 6 -methyl - IH - pyr idin - 2 - one N-{3- [3-Bromo-4- (2,4-difluoro-benzyloxy) -6-methyl-2-oxo2H-pyridin1 -ylmethyl ] -benzyl } -2 -hydroxy-acetamide ; 3-Bromo-4- (2,4-difluoro-benzyloxy) -6-methyl-i- [4- (piperidine-1carbonyl ) -benzyl] - iH-pyridin-2 -one ; 3-bromo-4- [ (2,4-difluorobenzyi) oxy] -i- (2,6- difluorophenyl) -6- [ (ethoxyamino) methyl] pyridin-2 (IH) -one 4- [3-Bromo-4- (2,4-difluoro-benzyloxy) -6-methyl-2-oxo-2Hpyridin1 - ylmethyl ] -Ni sopropyl - benzamide ; dif!uorobenzyl)oxy]-6-methy!-2-oxopyridin-l(2H)- yl]me hyl}benzamide hydrochloride; 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methy!-2- oxopyridin-l(2H)-yl]-N, 4-dimethylbenzamide; 4-[3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methy!-2-oxo-2Hpyridin-i-ylme hyl]-N,N-bis-(2-hydrox¥-ethyl)-benzamide; 3-Bromo-4-(2,4-dif!uoro-benz¥1oxy)-6-methyl-!- [4- (pyrrolidine-l-carbonyl)-benzyl]-iH-pyridin-2-one; 4-[3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyridin-l-y!methyl]-N-hydroxy-benzamide; 4-[3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyrldin-!-ylmethyl]-N-methyl-benzamide; 4-[3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2H- pyridzn-l-y!methyl]-N-(2-dimethylamino-ethyl)-benzamide; 3-bromo-4-[(2,4-difluorobenzyl)ox¥]-l-(iH-indazol-5ylmethyl)pyridin-2(IH)-one; 3-Bromo-4-(2,4-difluoro-benzy!oxy)-6-methyl-l- [4- (4methyl-piperazine-l-carbonyl)-benzyl]-iH-pyridin-2-one; 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-4-methylbenzaldehyde; 3-Bromo-4-(2,4-difluoro-benzyloxy)-l-(4dimethylaminomethyl-benzyl)-6-methyl-IH-pyridin-2-one; 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2- oxopyridin-l(2H)-yl]-N-(2-methoxyethyl)-4-methylbenzamide; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-[2-(dimethylamino)- 4,6-difluorophenyl]-6-methylpyridin-2(iH)-one hydrochloride; N-(2-aminoethyl)-4-{ [3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]methyl}benzamide hydrochloride; 4-[3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyridin-l-ylmethyl]-N-(2-hydroxy-ethyl)-benzamide; 3-Bromo-4-(2,4-difluoro-benzyloxy)-l-(4-hydroxymethyl- ({-me:hy!piperazin- !-y!) pheny!] - 6-methy!pyridin-2 (IH) -one ; 3-bromo-4- [(2,4-d=f!uorobenzy!)oxy]-i- [2- (dime hyiamino)- 4,6-d=fluorophenyl] -6-methy!pyridin-2 (!H) -one; 3-bromo-4- [(2,4-difiuorobenzyl)oxy] -!- [2,6-diflucrc-4- <4me hy!piperazin-!-y!)pheny1]-6-methy!pyridin-2(IH)-one; 4- [3-Bromo-4-(2,4-difiuoro-benzy!oxy)-6-methyl-2-oxo-2Hpyridin-!-ylmethyl]-N-(2-me%hoxy-ethy!)-benzamide; 3-5romo-4- (2,4-dif!uoro-benzyloxy)-!-{4-[(2-hydroxye%hy!amino)-methyl]-benzyl}-6-methyl-IH-pyridin-2-one; 3-bromo-4- [(2,4-dif!uorobenzyl)oxy]-l-(2,6difluorophenyi)-6-[(dimethylamino)methyl]pyridin-2(!H)-one; 3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-l-[2-methyl- {- (morpholin-4-vlcarbonyi)phenyl]pyridin-2(iH)-one; 3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-!-(4methylaminomethyl-benzyi)-iH-pyridin-2-one; 3-Bromo-4- (2,4-dlfluoro-benzyloxy)-6-methyi-!- [4- (morpholine-4-carbonyl)-benzyl]-iH-pyridin-2-one; N-(2-aminoethyl)-3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]benzamide; N-(3-aminopropyl)-3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]benzamide hydrochloride; 4-[3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyI-2-oxo-2H- pyridin-l-ylmethyl]-N-(2~methoxy-ethyl)-N-methyl-benzamide; l-(4-Aminomethyl-benzyl)-3-bromo-4-(2,4-dif!uorobenzyloxy)-6-methyl-IH-pyridin-2-one; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-[4- (piperazin-l-ylcarbonyl)benzyl]pyridin-2(IH)-one hydrochloride; 3-Bromo-4-(2,4-difluoro-benzyloxy)-l-[4-(isopropylaminomethyl)-benzyl]-6-methyl-IH-pyridin-2-one; dimethylpheny!) - 6-methylpyridin2 (IH) -one ; 3-Bromo-4- (2,4-difluoro-benzyloxy) -i- {3- [ (2-hydroxyethyl am!no) -methyl] -benzy! }- 6-methyliH-pyr idin-2-one ; !- (3-Aminomethyl-benzyl) -3-bromo-4- (2,4-difluorobenzy;oxy) - 6-methy!- iH-pyridin-2-one ; 3-Bromo-4- (2,4-dif!uoro-benzyloxy) -I- (4-hydroxy-benzv1) - 6-methylIH-pyridin-2-one; 3-chloro-4- [ (2,4-difluorobenzyl)oxy]-l- (2,6- difluorophenyl ) - 6 - [ (dimethylamino) methyl ] pyridin2 (iH) -one ; N- {3- [3-Bromo-4- (2,4-difluoro-benzyloxy) -6-methyl-2 -oxo2H-pyridinl-ylmethyl] -benzyl ] -acetamide ; 3-bromo-4- [(2,4-difluorobenzyl)oxy]-l-{2,6-difluoro-4- [ (2-hydroxyethyl) (methyl) amino] phenyl }-6-methylpyridin-2 (IH) - one ; ethyl 3- [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl ] benzoate ; i- [3- (aminomethyl)benzyl]-3-bromo-4- [(2,4difluorobenzyl)oxy]pyridin-2 (1H)-one trifluoroacetate; i- (3- { IBis- (2-hydroxy-ethyl) -amino] -methyl }-benzyl) -3bromo4 - (2,4 -di f luorobenzyloxy) - 6 -methyl - IH-pyridin2 -one ; 3-Bromo-4- (2,4-difluoro-benzyloxy) -I- [3- (isopropylaminomethyl ) -benzyl ] - 6 -methyl - iH-pyridin-2 -one ; {3- [3-Bromo-4- (2,4-difluoro-benzyloxy) -2-oxo-2H-pyridin- l-ylmethyl]-benzyl}-carbamic acid tert-butyl ester; 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl ] benzamide ; 3 - Bromo - 4 - ( 2,4 - di f i uoro - ben zyloxy) - 1 - [ 4 - ( 1 - hydroxy1 - methyl -ethyl) -benzyl] -6-methyl-IH-pyridin-2-one ; 3-Bromo-4- (2,4-difluoro-benzyloxy)-l- (3dimet hylaminomethyl - benzyl ) - IH-pyridin2 -one ; 3-Bromo-4- (2,4-difluoro-benzyloxy) -6-methyl-l- (3piperidin-l-ylmethy!-benzyl] -!H-pyridin-2-one; 3-bromo-4- [(2,4-d =_uoroo n -)oxy]-l2,6-= m 7 , " --,7 / dif!uorophenvl;-6_ ' - ( [(2 - methcxve=hvl)am=no] . . me_... \," _ } }_ =..- '- "'-': "' 2 (IH) -one; 3- [3-bromo-4- [ (2,4-difluorobenzy!)oxv] -6-me=hyl-2oxop,:'ridin- ! ( 2 H) -y! ] - N-methy!benzamide ; 3-bromo-4- [ (2,4-difiuorobezv!)oxy]-!-{2,4-dif!uoro-6- [ (2-hydroxyethyl) methyl) amino] phenyl }-6-methylpyridin-2 (!H) one ; 3Bromo-4- (2 4-dif!uoro-benzyloxy)-6-methyl-!-(3morpholin-4-ylmechyl-benzyl)-!H-pyridin-2-one; 3-bromo-l-(2,6-dimethylphenyl)-6-methyl-4-[ (2,4,6trifluorobenzyl) oxy] pyridin-2 (IH) -one ; 3-bromo-!- (2,6-dimethylpheny!)-6-methyl-4- [(2,4,6- =rifiuorobenzyl) oxy] pyridin-2 (IH) -one; l- (4-{ [Bis-(2-hydroxv-ethyl)-amino] -methyl}-benzyl)-3bromo-4-(2,4-dif!uoro-benzyloxy)-6-methvl-iH-pyridin-2-one; B-bromo-4- [(2,4-difluorobenzyi)oxy] -i- (2,6-dif!uoro-4morpholin-4-ylphenyl) - 6-methylpyridin-2 (ill) -one ; 4-Benzyloxy-3-bromo-l- (4fluoro-benzyl) - IH-pyridin-2-one; 4-[3-Chloro-4-(2,4-difluoro-benzyloxy)-2-oxo-2H-pyridinl-ylmethyl]-benzamide; 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-N,N, 4-trimethylbenzamide; 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-N-isopropylbenzamide; 4-[3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyridin-l-ylmethyl]-benzamide; 3- [3-Bromo-4- (2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyridin-l-ylmethyl]-benzonitrile; 3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-l-(3piperazin-l-y!methyl-benzyl)-iH-pyridin-2-one; pyridin-l-ylmethyl]-N-(2-hydroxy-ethyl)-N-methyl-benzamide; methyl 4-[3-bromo-4-[(2,4-difluorobenzyi)oxy]-6-methyl-2oxopyridin-l(2H)-y!]-3-chlorobenzoate; 3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-l- [3- (morpholine-4-carbonyl)-benzyl]-!H-pyridin-2-one; 3_[3_Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyridin-l-ylmethy!]-N,N-bis-(2-hydroxy-ethyl)-benzamide; 4_ [3-Bromo-4-(2,4-dif!uoro-benzyloxy)-6-methy!-2-oxo-2H- pyridin-l-ylmethyi]-benzoic acid methyl ester; 3-[3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyridin-l-ylmethyl]-N-hydroxy-benzamide; 3-Bromo-4-(2,4-difluoro-benzyloxy)-l-(3-hydroxymethylbenzyl)-6-me hy!-iH-pyridin-2-one; 3-bromo-4- [(2,4-dif!uorobenzyl)oxy]-l-(3fluorobenzyl)pyridin-2(iH)-one; 3-Bromo-4-(2,4-dif!uoro-benzyloxy)-l-(3-fluoro-benzyl)- IH-pyridin-2-one; N-{3- [3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo- 2H-pyridin-l-ylmethyl]-benzyl}-methanesulfonamide; 3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-l-[3- (pyrrolidine-l-carbonyl)-benzyl]-iH-pyridin-2-one; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-(pyridin3 -ylmethyl ) pyridin2 (IH) -one ; N- (3-aminopropyl) -3- { [3-bromo-4 - [ (2,4difluorobenzyl) oxy] -6-methyl-2-oxopyridin-i (2H) - yl]methyl}benzamide hydrochloride; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-(pyridin3-ylmethyl)pyridin-2(iH)-one; 3-Bromo-4-(2,4-difluoro-benzyloxy)-l-(3methylaminomethyl-benzyl)-iH-pyridin-2-one; oxopyridin-I (2H) -y!] -3,5-dichlorobenzenesui fonamide; 3 bromo-4 [(2 -dif! - = TvT cx<j .. i -! - [4 -,'dimethviamino) - 2 £ -di_,-orooh -.y-= = i ]- -methv_D\,,-'.4:m ....-p ".n, ' .... ; 3Bromo-a- . (2,4-di _= o-o.n x )-6-me--h.vl:'''- " = "' ....- - - ' 4- ioeridin-i-ylmethvl-b=n \'' -iH-mvr'_din-2-one; 3-Promo-4- [(2,4-difluorobenzyl)oxy] -!- {pyrldin--.- ylme,thyl) pyridin-2 (ill) -one; N- (2-aminoethyl) -3-{ [3-bromo-4- [ (2,4-dif!uerobenzyl)oxv - 6-meLhyl-2-oxopyridin-! (2H)-y!]methyl)benzamide hydroch!oride; 3-bromo-l- [2-chloro-5- (hydrox>Tnethyl)pheny!] -4- [ (2,4di f!uorobenzy! ) oxy] -6-methylpyridin-2 (!H) -one; 3-bromo-4- [(2,4-difluorobenzy!)oxy]-l- (2,6difluorophenyl) - 6-me hylpyridin-2 (IH) -one ; 3-chloro-l- [2-chloro-5- (hydroxymethyl)phenyl]-4- [(2,4- difiuorobenzyl)oxy]-6-methylpyridin-2 (!H) -one; 3- [3-bromo-4- [(2,4-difluorobenzyi)oxy]-6-methyl-2oxopyridin1 (2H) -yl] -N- (2-hydroxyethy!) -4-methy!benzamide; 2-{3- [3-Bromo-4- (2,4-difluoro-benzyloxy) -2-oxo-2Hpyridinl-ylmethyl ] -phenyl } -acetamide ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [3- (piperazinl-ylcarbonyl) benzyl] pyridin-2 (IH) -one hydrochl oride ; 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l- (2,6di f luorophenyl ) - 6 - methylpyridin2 (IH) - one ; 4- [3-Bromo-4- (2,4-difluoro-benzyloxy) -2-oxo-2H-pyridin-lylmethyl]-benzoic acid methyl ester; I- (3-Aminomethyl-2-fluoro-benzyl]-3-bromo-4- (2,4di f luoro-benzyl oxy) - IH -pyri din2 -one ; 3-bromo-4- [(2,4-difluorobenzyl)oxy]-l- (2,6- difluorophenyl) -6- (morpholin-4-ylmethyl) pyridin2 (IH) -one ; 4- (benzyloxy) -3-bromo-l- (4-fluorobenzyl)pyridin-2 (IH) - y!methyl) pyridin-2 (IH) -one ; !- [3- (aminomethyl)benzyl]-3-bromo-4- [(4f!uorobenzyl)oxy]pyridin-2 (iH)-one trifluoroacetate; i- [3- (2-aminoethyl)benzyl] -3-bromo-4- [(2,4difluorobenzyl)cxy]pyr din-2 (!H) -one rifluoroacetate; I- [3- (aminomethy!)benzyl]-3-bromo-{- [(4f iuorobenzy!) oxy] pyridin-2 (IH) -one ; 3-bromo-!- (2,6-dich!orophenyl)-4- [(2,4- difluorobenzyl) oxy] -6-methylpyridin-2 (IH) -one; 3- [3-bromo-4- [(2,4-dif!uorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl] -N- (2-hydroxyethyl) benzamide ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-l- (pyridin4-ylmethyl) pyridin2 (IH) -one ; 3-Bromo-4- (2,4-dif!uoro-benzyloxy)-i- (4-methoxy-benzyl)- 6-methyl-iH-pyridin-2-one; 4- [3-Bromo-4- (2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyridin-!-ylmethyl] -N, N-dimethyl-benzamide ; 3 -bromo-6-methy1 - i- (pyridin-4 -ylmethyl) -4 - [ (2,4,6- trifluorobenzyl) oxy] pyridin-2 (IH) -one; 4- [3-Bromo-4- (2,4-difluoro-benzyloxy) -2-oxo-2H-pyridin-iylme thyl ] - benzamide ; 3- [3-Bromo-4- (2,4-difluoro-benzyloxy) -6-methyl-2-oxo-2Hpyridin1 -ylmethyl ] -N-methyl -benzamide ; { 3- [3-Bromo-4- (2,4-difluoro-benzyloxy) -6 -methyl -2-oxo-2Hpyridin-l-ylmethyl]-benzyl}-carbamic acid methyl ester; 3-bromo-4- [ (2,6-difluorobenzyl) oxy] -I- (2,6dimethylphenyl ) - 6 -met hylpyridin2 (IH) -one ; 4- [3-Bromo-4- (2,4-difluoro-benzyloxy) -6 -methyl -2-oxo-2H- pyridinl-ylmethyl] -benzonitrile ; l-Benzyl-4-benzy!oxy-3-bromo-6-methy!-!H-pyridin-2-one; l_benzyl_4_(benzyicxy)_3_bromc-6- =- ,: - ........ !-Benzyl-3-bromo-4-(2,4-difluoro-benzv!oxy)-6-me-hyi-lH- PY-- e--=-2-one; {3- [3-Bromo-4- (2,4-dlf!uoro-benzyioxy) -2-oxo-2H-pyri!zn- !-ylmethy!]-pheny!}-acetonitriie; 3- [3-Bromo-4- (2,4-dif!uoro-benzyioxy)-6-me hy!-2-oxo-2Hpyridin-!-y!methy!]-N-(2-hydroxy-echyl)-benzamide; 3-Chloro-4-(2,4-difluoro-benzy!oxy)-l- (3-fiuoro-benzy!}- IH-pyrldin-2-one; l-Allyl-3-chloro-4-(2,4-dif!uoro-benzyloxy)-6-menhyl-IHpyridin-2-3ne; 3-Chloro-4-(2,4-difluoro-benzy!oxy)-l-[4-(isopropylamino- methy!)-benzyl]-iH-pyridin-2-one; methyl 3-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-menhyl2-oxopyridin-l(2H)-yl]-4-methyibenzoate; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-l- (2,4,6-trifluorophenyl)pyridin-2(iH)-one; 3-Bromo-4-(2,4-dif!uoro-benzyloxy)-6-methyl-l-(4piperazin-l-ylmethyl-benzyl)-iH-pyridin-2-one; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l- (2,6difluorophenyl)-6-(hydroxymethyl)pyridin-2(IH)-one; 3-[3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2H- pyridin-l-ylmethyl]-N,N-dimethyl-benzamide; 3-bromo-l-(3-fluorobenzyl)-4-[(3methylbenzyl)oxy]pyridin-2(IH)-one; 3-Bromo-l-(3-fluoro-benzyl)-4-(3-methyl-benzyloxy)-IH9yridin-2-one; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-(l,2,3,4tetrahydroisoquinolin-5-ylmethyl)pyridin-2(iH)-one; methylbenzy! ) oxy] pyridin2 (IH) -one ; 3-chloro-4- [(2,4-difluorobenzvl)oxy]-l-(isoquine!in-- - ylmethy!)pyridin-2(IH)-one trifluoroaceta%e; 3- [3-Bromo-4- (2,4-dif!uoro-benzyloxy) -6-methyl -2-oxo--0H pyridin-!-ylmethyl ] -benzamide ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- ( { 5- [ (:: me hylpiperazin1 -y! ) carbony! ] pyrazin2 -yi }methyl ) pyr zdin2(!H)-one trif!uoroacetate; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -i- [5- (hydroxymethyl) 2-me hylphenyl] -6-methylpyridin-2 (ill) -one; l-allyl-3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6methy!pyridin-2 (IH) -one ; 3-bromo-4- [(2,4-difluorobenzyi)oxy] -i- (pyridin-3ylmethyl) pyridin-2 (IH) -one ; 3 - bromo4 - [ ( 2,4 - d i f i uoroben zyl ) oxy ] - 1 - ( 2 - me t hoxy - 6 - methylphenyl) - 6-methylpyridin-2 (IH) -one ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -I- (2-methoxy-6methylphenyl) - 6-methylpyridin2 (IH) -one ; 3- [3-Bromo-4~ (2,4-difluoro-benzyloxy) -2-oxo-2H-pyridin-l- ylmethyl] -benzamide; 3 -chloro4 - [ ( 2,4 -difluorobenzyl ) oxy] - 6 - (hydroxymethyl) (2,4,6-trifluorophenyl) pyridin-2 (IH) -one; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [2- ( tri f luoromethyl ) phenyl ] pyridin2 (IH) - one ; 4- [3-Bromo-4- (2,4-difluoro-benzyloxy) -6 -methyl -2-oxo-2Hpyridin-l-ylmethyl]-benzoic acid; 3-Bromo-4- (2,4-difluoro-benzyloxy) -6-methylI- (4morphol in4 -ylmet hyl - benzyl ) - iH-pyridin - 2 - one ; 4- (2,4-Difluoro-benzyloxy) - I- (3fluoro-benzyl) -3iodo- pyridin2-one ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-l- (2,4,6trifluorophenyl) pyridin-2 (IH) -one; oxopyridin- ! (2H) -y! ] -N-hydroxybenzamiie ; 3-bromo-i- (2,6-dichlorophen'/l) -4- [ (2,6d f!uorobenzyl) oxy] - 6-mes-hylpyridin2 (!H) -one ; 3- (4-Benzy!oxy3-bromo2-oxo-2H-D\:r -a-,.-_ -','=metnv- ' b n_o itriie ; 3-b'_-omo-4 [(2,4 dif!aorobenzvi]oxv] { m= o - - [3- (pyrrolidinl-yicarbony!) phenyi] pyridin-2 (IH) -one ; 3-bromo-4- [ (2,4-difluorobenzyi) oxy] -l- (2fluorobenzyl) pyridin-2 (1H) -one ; 4- (benzyloxy) -3 -bromoi- (4-methylbenzyl) pyridin2 (IH) one ; 3-{ [3-chloro-4- [(2,4-difluorobenzy!)amino]-6-methyl-2oxopyridin- ! (2H) -y!] methyl }benzonitrile; 3- [3-Bromo-4- (2,4-dif!uoro-benzy!oxy)-6-methyl-2-oxo-2Hpyridin- !-y!methyl] -N-isopropyl-benzamide; 3-bromo-!- (4-bromo-2,6-difluorophenyl)-4- [(2,4di fluorobenzyl) oxy] -6-methylpyridin-2 (IH) -one ; 3-bromo-4- [ (4fluorobenzyl) oxy] -6-methyli- (pyridin-3- ylmethyl) pyridin-2( 1 H) - one ; 3 - bromo4 - [ ( 4-fluorobenzy!) oxy] -6-methyli- (pyridin-4ylme thyl ) pyridin2( 1 H) - one ; 3-bromo-4- [ (4f luorobenzyl ) oxy] - 6 -methyl - 1 - (pyridinylme thyl ) pyridin - 2(1H) -one ; 4- (benzyloxy)-3-bromoi- (4-chlorobenzyl) pyridin-2 (IH) one ; 4 - Benzyloxy3 -bromo1 - ( 4 - chlorobenzyl ) - IHpyridin3 -bromo-l- (4-fluorobenzyl) -4- [ (4fluorobenzyl) oxy] pyridin-2 (IH) -one ; 3-bromo-l- (2,6-dichlorophenyl) -4- [ (4-fluorobenzyl) oxy] methylpyridin-2 (IH) -one; 3-Bromo-l- (4fluoro-benzyl) -4- (4fluoro-benzyloxy) - pyridin2 -one ; methyl 4- [3-bromo-4- [(2,4-dif!uorobenzyl)oxy]-6-methy!-2oxopyridin1 (2H) -yl] benzoate ; 4- (4-Benzyloxy3-bromo-2-oxo-2H-pyridini-vlmethy! benzoic acid; 4-{ [4- (benzyloxy) -3-bromo-2-oxopyridin-! (2H)- yl]methyl}benzoic acid; 3-ch!oro-4- [(2,4-difluorobenzyl)oxv] -6-methyl-l- (2 4,6trifluoropheny! ) p vridin2 (!H) -one ; 4- (benzyloxy) -3-bromo-l- (2f!uorobenzyl) pyridin-2 (IH) - orie ; 3-chloro-4- [(2,4-dif!uorobenzyl)oxy]-l- (2,6di f!uorophenyl) -6- (hydroxymethyl) pyridin-2 (IH) -one; N- (2-aminoethyl)-4- [3-bromo-4- [(2,4-difluorobenzyl)oxy] - 6-methy!-2-oxopyridin-! (2H)-yl]benzamide hydrochloride; 4-Benzyloxy-3-bromo-l- (4-methylsul fanyl-benzy!) -IHpyrtdin2-one ; l-Benzyl-4-benzyloxy3-chloro1H-pyridin-2-one ; 4- (benzy!oxy) -3-promo-l- [4- (methylthio)benzyl]pyridin2 IH) -one ; 1 -benzyl4- (benzyloxy) -3-chloropyridin-2 (IH) -one ; 3 -bromo-4- [ (2,4-difluorobenzyl) oxy] -I- { [5- (hydroxyme t hyl) pyrazin-2 -yl ] methyl } - 6 -methylpyridin2 (IH) -one 3 - bromo1- (2,6-dimethylphenyl) -4- [ (4fluorobenzyl) oxy] -6methylpyridin2( 1 H) - one ; 3 - bromo - 1 -(2,6-dimethylphenyl) -4- [ (4-fluorobenzyl) oxy] -6methylpyridin2( 1 H) - one ; 3 -Bromo4 - ( 2,4 -di f luoro-benzyloxy) - 1 - [3 - ( isopropylaminomethyl ) -benzyl ] - iH-pyridin-2 -one ; 3- [3-Chloro-4- (2,4-difluoro-benzyloxy) -2-oxo-2H-pyridin1 -ylmethyl ] - 2 - f luoro-benzamide ; oxopyridin-! (2H) -yl] methyl }-N- (2,3-dihydroxyp. ropyl) pyraz =-0carboxamide ; {3- [3-Bromo-4- (2 -dif!uoro-benzy!cxy)-2-oxo-2H-pvrid n- !-ylmethyl]-phenyl}-acetic acid ethyl ester; 4- (4-Benzyloxy3-bromo2-©xo2H-pyr!din- !-y!methyl ! -Xhydroxy-benzamidine ; 4- { [4- (benzyloxy) -3-bromo-2-exopyridin1 (2H) -y!] ,meth':'i } - N' - hydroxyben=enecarboximidamide ; ethyl 5-{ [3-chloro-4- [(2,4-difluorobenzy!)oxv] -6-methv!- 2-oxopyridin-l(2H)-yi]methyl}pyrazine-2-carboxylate; 3-Bromo-4- (2,4-difluoro-benzy!oxy) - i- (3-methoxy-benzyi) - !H-pyre-din2-one ; 3-bromo-4 - [ (2,4-diflu©robenzyl) oxy] - 6-methylI- [ (5methylpyra--!n2-yl) methyl] pyridin-2 (IH) -one ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] - !- (3methoxybenzyl) pyridin-2 (IH) -one ; 4- (4-Benzyloxy-3-bromo-2-oxo-2H-pyridinl-ylmethyl) - benzoic acid methyl ester; 3-Bromo-4- (2,4-difluoro-ben:y!oxy) - i- (4 - dimethylaminomethyl-benzyl) -IH-pyridin-2-one; 3-Chloro-4- (2,4-difluoro~benzyloxy) -i- (3-methanesulfonylbenzyl ) - iH-pyridin-2 -one ; 4 - (4 -Benzyloxy3 -bromo2 -oxo2H-pyridin1 -ylmethyl ) - benzoic acid methyl ester; methyl 4- { [4 - (benzyloxy) -3-bromo-2-oxopyridin1 (2H) - yl] methyl}benzoate; ethyl 5-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyr i d i n - 1 ( 2 H) - yl ] me t hyl } pyra z i ne - 2 - c a rboxyl a t e ; 4-{ [4- (benzyloxy) -3-bromo-2-oxopyridin-1 (2H) - yl] methyl }benzonitrile; 4 - (4 - Benzyloxy3 - bromo2 -oxo2H-pyridin1 - ylmethyl ) - benzonitrile ; { 3- [3-Bromo-4- (4 - f!uoro-benzy!oxy) - 2-oxo-2H-pyrzdin- !- ylmethy!]-benzy!}-carbamic acid er obutylester; 3-bromo-4- [ (2,4-difluoroben=yl) oxy] -I- [5- (l-hydro×yi- methylethyl) -2-methylphenyl] -6-methylpyridin-2 (IH)-one; 4 - (benzylox-i) -3-bromoI- (2,6-dichloropheny!) -6methylpyridin2 (!H) -one ; !- (3-Aminomethyl -benzyl) -4-benzyloxy-3-bromo- !H-pyridin2 -one ; 3-bromo-4- [(4-fluorobenzyl)oxy]-l- (pyridin-4- ylmethyl)pyridin-2 (iH)-one; 4- (benzyloxy) - 3-bromoI- (4-bromobenzyl) pyridin-2 (IH) -one 4-Benzy!oxy3-bromoI- (4-bromo-benzyl) - iH-pyridin-2-one 5-bromo-4- [(2,4-difluorobenzyl)oxy]-l-(2,6di f luorophenyl ) - 6 -oxoI, 6 -dihydropyridine - 2 - carbal dehyde ; 3-chloro-4- [ (2,4-difluorobenzyl)oxy]-l-{ [5- (hydroxymethyl) pyrazin2-yl] methyl }- 6-methylpyridin-2 (IH) -one 4- (4-Benzyloxy-3-bromo-2-oxo-2H-pyridinl-ylmethyl) - benzamide ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methylI- [3- (piperazin-l-ylcarbonyl)phenyl] pyridin-2 (IH) -one hydrochl ori de ; 3-bromo-4- [ (2,4-difluorobenzyl) amino] -i- (3f luorobenzyl ) pyridin-2 (IH) -one ; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [ (5- methylpyrazin-2-yl) methyl] pyridin-2 (IH) -one; 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -I- [5- (hydroxymethyl) - 2 -methylphenyl ] - 6 - methylpyridin2 (IH) - one ; 3-bromo-l- (3fluorobenzyl) -4- [ (4f luorobenzyl ) oxy] pyridin2 (IH) -one ; 3-Bromoi- (3fluoro-benzyl) -4- (4fluoro-benzyloxy) - IHpyridin-2-one ; (morpholin-4-ylcarbonyl)phenyl]. ' DV_IQ_n "{ - 2( !H) -one ; 3- (4-Benzyloxy.-3-bromo-2-oxc-2H-pyr!din-l-y!methyi) - benzoic acid methyl ester-; 3-bromo-!- (3-fluorobenzy!)-4-{ [2hydroxyme:hy!) benzyi ] oxy} py -idin2 (IH) -one ; 3-BromoI- (3f!uoro-benzyi) -4- (2-hydroxymethy!- menzyloxy) - iH-pyridin-2-one ; l-Be-nzo [i, 3] dioxoi-5-yimeLhyl-3-bromo-4- (2,4-dif!uorobenzyloxy) - iH-pyridin2-one ; 3-bromo-4- [ (2,6-difluorobenzy!)oxy] -6-methyl-l- (p}'ridin4-ylmethyl) pyridin-2 (ill) -one ; 3-bromo-4- [(3-chlorobenzyl)oxy]-l- (3f luorobenzyl) pyridin-2 (IH) -one; 3-bromo-4- [(3-chlorobenzyl)oxy]-l- (3fluorobenzyl) pyridin-2 (IH) -one; 3-Bromo-4 - (3ch!oro-benzyloxy) - I- (3fluoro-benzyl ) - IHpyridin-2-one; 4- (benzyloxy) -3-bromoi- (3fl'aorobenzyl) pyridin2 (1H) - one ; 4 - Benzyl oxy3 -bromo1 - ( 3 - f luoro - benzyl ) - IH - pyridin - 2 - one ; 3-Bromo-4- (2,4-difluoro-benzyloxy) -6-methyl-i- [3- (piperidi ne - 1 ~ carbonyl ) - benzyl ] - IH-pyridin2 -one ; 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl ] -N, N-dimethylbenzamide ; 3- [3-Chloro-4- (2,4-difluoro-benzyloxy) -2-oxo-2H-pyridinl-ylmethyl]-2-fluoro-benzoic acid methyl ester; i- (3fluorobenzyl) -4- [ (4-fluorobenzyl)oxy] -3iodopyridin2 (IH)-one; i- (3-Fluoro-benzyl) -4- (4f!uoro-benzyloxy) -3 - iodoIHpyridin2 -one ; N- (3-aminopropyl -4- [3-bromo-4- [(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-i (2H)-yl]benzamide hydrochloride; 4- { [3-bromo-4- [ (4f!uorobenzyl) oxy] -2-oxopyridinl (2H} - y!] methyl }benzonitrile; 4- [3-Bromo-4- (4-fluoro-ben-y!oxy)-2-oxo-2H-pyridin-lylmethyl] -benzonitrile ; 3-Bromo-l- (3-fluoro-benzyl) -4- (2,3,4-trifluorobenzyloxy) - iH-pyridin-2-one ; !-benzyl-4- (ben=ylo c!) - 3-bromopyridin2 (!H) -one; 5-{ [3-bromo-4- [(2,4-dif!uorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl] methyl }-N- (2-hydroxyethyl) -N- methylpyrazine-2-carboxamide ; 4- (4-Benzy!oxy3-bromo2-oxo-2H-pyridinl-ylmethyl) - benzonitrile ; 3-bromo-l- (2, 4-dif!uorobenzyl) -4- [(2,4difluorobenzyl) oxy] pyridin-2 (IH) -one ; 3-Bromo-l- (2,4-difluoro-benzyl) -4- (2,4-difluorobenzyloxy) - !H-pyridin-2-one ; 4- [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyi-2oxopyridin1 (2H) -yl] -N- (2-hydroxyethyl) benzamide ; 3-bromo-4- [ (4fluorobenzyl) oxy] - I- (pyridin-3- ylmethyl) pyridin-2 (IH) -one ; 1 - Benzyl - 4 - ben zyl oxy3 - bromo - 1 Hpyri din - 2 - one ; 3 -bromo1 - (cyclopropylmethyl) -4 - [ (2,4 - difluorobenzyl ) oxy] -6-methylpyridin-2 (IH) -one ; 1 - (4 -Aminomethyl - benzyl ) -4 - benzyloxy3 - bromoiM-pyridin- 2-one ; 3-bromoi- (4-fiuorobenzyl) -4- [ (4-fluorobenzyl) amino] -6methylpyridin2 (IH) -one ; 3- [3-Bromo-4- (2,4-difluoro-benzyloxy) -6-methyl-2-oxo-2Hpyridin-l-ylmethyl]-benzoic acid methyl ester; 5- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-2oxopyridin1 (2H) -yl ] methyl } -N, Ndimet hylpyrazine - 2 - carboxamide ; 3-bromo-4- [ (4f!uorobenzyl) oxy] -6-methyl-!- (pyri/in-iylmethyl) cyridin-2 (!H) -one ; 3-bromo-4-[(2,4-difluorobenzy!)oxy]-i- (2,6- /-methylphenyl) - 6-methylpyridin-2 (IH) -one ; 3-bromo-!- (2,6-dichlcrophenyl)-4- [(2,4difluorobenzv!) oxy] - 6-meshylpyr idin-2 (!H) -one ; 4- (ben=y!oxy)-l- (4-bromobenzyl)pyridzn-2 (iH)-one; 3-bromo-4-hydroxyI- (4-hydroxybenzyl) pyridin2 (IH) -one ; 4 - (benzy!oxy) - 3-bromo-!- [2- (trifiuoromethyl)benzy!]pyridin-2(!H)-one; l-benzy!- - [ (3-chlorobenzyl) oxy] - 6-methy!pyridin2 (!H) - one ; 4- (benzy!oxy) -3-bromo-!- (piperidin-3-ylmethyl) pyridin2 (IH) -one hydrochloride; !-benzy!-3-bromo-2-oxoi, 2-dihydropyridin-4-yl methyl (phenyl) carbamate ; 4- (ben:ylamino) -i- (3fluorobenzyl) - 6-methyl-3nitropyridin-2 (IH) -one ; ert-butyl 4- [3-bromo-l- (3-fluorobenzyl) -2-oxo-i,2- dihydropyridin4 -yl ] piperazineI- carboxy!at e ; ethyl [4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl] acetate; N- [ 3 - bromo1 - ( 3 - f luorobenzyl ) - 2 - oxo - i, 2 - dihydropyridinyl ] benzenesul fonamide ; 3-bromo-4- [ (4-tert-butylbenzyl)oxy]-l- (3fluorobenzyl) pyridin-2 (IH) -one ; N- [3 -bromo1 - ( 3 - f l uorobenzyl) - 2 -oxoi, 2 -dihydropyr i di ny! ] - 1 -phenylmethanesul fonamide ; I- (biphenyl-2-ylmethyl) - 3-bromo-4- [ (4- fluorobenzyl) oxy] pyridin-2 (IH) -one; 4- (biphenyl-2-ylmethoxy) -3-bromoi- (3fluorobenzyl) pyridin-2 (IH) -one ; methyl -{ [3-bromo-l-(3 fluorobenzy!)-2-oxo-i 2- dihyd opyridin-4-y!] amino}benzoate; 3-bromo-!- (3-fluorobenzy!)-4- [(3,4,5trimethoxyphenyl ) amino pyridin-2 (IH) -one ; 3-bromo-l° (3-fluorobenzyl) -4- [4- (4fluorophenyl) piperazin- !-yl ] pyridin-2 (IH) -one ; 3-bromoI- (3fluorobenzy!) -4- (4-methylpiperazznl- yl)pyridin-2(iH)-one trifluoroacetate; N- [3-bromo-l- (3fluorobenzy!) -2-ohoI, 2-dihydropyridin-4y!] -2,5-dif!uorobenzamide ; N- [3-bromoi- (3fluorobenzyl) -2-oxoi, 2-dihydropyridin-4- yl]-2,4-difluorobenzamide; 3-bromoi- (cyclohexylmethyl) -4- [ (4fluorobenzyl) oxy] pyridin-2 (!H) -one; 3- [4- (benzyloxy) - 3-bromo-2-oxopyridinl (2H) -yl ] propanoic acid; N- [ 3 - bromo1 - ( 3 - f luo robenzyl ) - 2 - oxo - i, 2 - di hydropyridin - 4 - yl] -N' - (2,4-difluorophenyl) urea; 3- [4- (benzyloxy) -3-bromo-2-oxopyridin-i (2H) - yl ] propanamide ; 4 - (benzyloxy) - 3 - bromo - 1 - ( 3 - morphol in4 - yl - 3 - oxopropyl ) pyridin-2 (IH) -one ; N- ( 3 - aminopropyl ) - 3 - [ 4 - ( benzyl oxy) - 3 - bromo - 2 - oxopyridin1 (2H) -yl ] propanamide hydrochloride ; 4 - (benzyloxy) -3 -bromo1 - (3 -oxo3 -piperazin1 - ylpropyl ) pyridin2 (IH) -one hydrochloride ; 4 - (benzyloxy) - 3 -bromo1 - ( 2 - morphol in4 -ylethyl ) pyridin- (trifluoromethyl) benzyl ] amino}pyridin-2 (IH) -one ; N-{2-aminoethy!)-3- [4-(ben=y!oxy) -3-brcmo-2-oxcpyrid=nl(2H)-y!]propanam=de hydrochloride; [3-bromo-4- [(2,4-dif!uorobenzyl)cxy]-6-me=hyl-2- oxopyridin-I (2H) -yl]acetic acid; 3 -bromo-4- [ (2,4 -di fluorobenzvl } oxy] - 6-methyl - !- (tetrahydrofuran-2-y!methyl) pyridin2 (!H) -one ; 4- [ (2,4-difluorobenzyl) oxy] ~6-methyl- !- (zetrab.vdrofuran2-ylmethyl) pyridin-2 (!H) -one ; mezhyl 3-bromo-4- [ (2,4-difluorobenzyl)ox),] -6-methyl-2oxopyridine1 (2H) -carboxylate ; l-al!yl-3- (2 0 4-difiuorobenzyl)-4- [(2,4difluoroben-y!) oxy] -6-methylpyridin-2 (IH) -one ; 4- (benzyloxy) -!- (2,2-diethoxyethyl) pyridin-2 (ill) -one methyl N-acetyl-3- [4- (benzyloxy)-2-oxcpyridin-l(2H)- yl] alaninate ; benzyl N-acetyi-3- [4- (benzvioxy)-2-oxopyridin-i(2H)- yl] alaninate ; benzyl N- [(benzyloxy) carbonyl]-3- [4- (benzyloxy)-2- oxopyridin1 (2H) -yl] alaninate ; 4 - (benzyl oxy) - 1 - ( 2 - oxopropyl ) pyri di n2 ( 1 H) - one ; 5- { [4- (benzyloxy) -2-oxopyridin-i (2H) -yl] methyl}-5methylimidazol idine-2,4 -dione ; ethyl [4- (benzyloxy)-2-oxopyridin-l(2H)~yl]acetate; 2- [4- (benzyloxy) -2-oxopyridin-i (2H) -yl] acetamide ; l-benzyl-4- (benzyloxy) -3,5-dibromopyridin-2 (IH) -one ; 4- (benzyloxy) - l-ethylpyridin2 (IH) -one; 4- (benzyloxy) -I- (4-[er -butylbenzyl)pyridin-2 (IH) -one; 4- { [4- (benzyloxy) -2-oxopyridin-i (2H) - yl] methyl }benzonitrile ; tert-butyl 3-{ [4- (benzyloxy}-2-oxopyridin-i(2H)- yl ] methyl } piperidine1 - carboxyl ate ; i, 3 - dibenzyl - 4 - hydroxy6 - me t hylpyridin2 (IH) - one ; l-benzyl-6-methyl-2-oxo-l, 2-dihydrepyridln-4 -yl methanesul fonate; 4- (benzyloxy) - I- (4-brom.obenzyl) pyridin-2 (IH) -one ; 4- (benzyloxy) -3-bromopyridin-2 (IH) -one ; 4- (benzyloxy) -3-promo-l- [2- (-rlfluoromethyl) benzyl] pyridin-2 (!H) -one ; l-benzyl-4- (l-naphthylmethoxy) pyridin2 (!H) -one ; l-benzyl-4- (benzylthio) - 3,5-dibromopyridin-2 (IH) -one ; l-benzyl-4- [ (2,6-dichlorobenzyl) oxy] pyridin-2 (IH) -one ; l-benzyl-3- [ (benzylamino) methyl] -4- (benzyloxy) pyridin2 (IH)-one; l-benzyl-4- (benzyloxy) -3- { [ (2cyc!ohexylethyl) amino] methy! }pyridin2 (iH} -one ; l-benzyl-4- (benzylthio) - 5-methylpyridin-2 (IH) -one ; l-benzyl-3-brome-6-methyl-2-oxoi, 2-dihydropyridin-4-yl methanesul f onate ; l-benzyl-3-bromo-6-methyl-4- { [2- (trifluoromethyl) benzyl] oxy}pyridin-2 (IH) -one ; l-benzyl-6-methyl-2-oxo-l, 2-dihydropyridin-4-yl 4bromobenzenesul fonate ; i - benzyl - 4 - [ ( 3 - chl orobenzyl ) oxy] - 6 -methylpyridin2 (IH) - One ; 1 -benzyl - 3 - bromo6 -methyl -2 - oxol, 2 - dihydropyridin4 -yl 4-bromobenzenesulfonate ; 4-phenoxy-l- { [2- (trimethylsilyl) ethoxy] methyl }pyridin2 (iH)-one; l-benzy1-4 -phenoxypyridin2 (IH) -one ; 1 - (4 -methoxybenzyl ) - 4 -phenoxypyridin2 (IH) - one ; 3 - bromo - 4 - hydroxy1 - ( 4 - hydroxyben zyl ) pyr i di n2 ( 1 H) - one hydrochloride ; 4 - (benzyl oxy) - 3 -bromo-1 - (piperidin3 -ylmethyl ) pyridin- !-benzyl-4- [ (2,6-dich!orobenzyl) oxy] pyridin2 (1B') -one ; l-benzyl-4- (benzy!oxy)-3,5-dibromopyridzn-2 iH)-one; 3-bromo-!- (3-fluorobenzyl)-4- [(E)-2- (4fluorophenyl) viny!] pyridin-2 (IH) -one ; !-benzy!-4- (benzyloxy) -2-oxoI, 2-dihydropyrzdine-3 - carba!dehyde ; l-benzyl-4- (benzy!oxy) pyridin-2 (IH) -one ; !-benzyl-4- (benzy!oxy) pyridin2 (IH) -one ; l-benzyl4- (benzylthio) pyridin2 (!H) -one ; methyl 4- [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -2oxopyridin1 (2H) -yl] benzoate ; benzyl (5-nitro-2,6-dioxo-3,6-dihydropyrimidin-i (2H)- yl) acetate; ethyl 3-bromo-4- [ (2,4-difluorobenzyl)oxy]-6-methyl-2-oxo2H1,2 ' -bipyridine5 ' -carboxylate ; 4- (benzyloxy) - I- (4-methylbenzyl) pyridin-2 (IH) -one; [5-bromo-4- [(2,4-difluorobenzyl)oxy]-l- (2,6dif luoropheny! ) - 2 -methyl - 6 -oxo1,6 - dihydropyridin3 -yl ] methyl carbamat e ; 4 - ( benzyl oxy) - 1 - ( 4 - chl orobenzyl ) pyr i di n2 ( 1 H) - one ; methyl (2E)-4- [4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin-I (2H) -yl ] but -2-enoate ; 4 - (benzyloxy) - 1 - ( 2 - fluorobenzyl) pyridin2 (IH) -one ; tert-butyl 4-{ [4- (benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl] methyl }piperidinel-carboxylate ; 4- (benzyloxy) - I- (3fluorobenzyl) pyridin-2 (IH) -one ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] - I- (2,6difluorophenyl) -5- (I, 2-dihydroxyethyl) -6-methylpyridin-2 (IH) - one ; 1 - benzy1-4 - hydroxy6 -methylpyridin2 (IH) -one ; 4 - ( { [3 -bromo1 - ( 3 - fluorobenzyl ) - 2 -oxoI, 2 -dihydropyridin4 -yl ] oxy} methyl ) benzoni trike ; l-benzyl-4- (benzyloxy) -6-methyipyridin-2 (IH) -one; 5-bromo-4- [ (2,4-difluorobenzyl)oxy] -i- (2,6difiuorophenyl) -2-methy!-6-oxo-l, 6-dihydrepyridine-3 carbaldehyde oxide; l-benzyl-4- (benzy!thio) -3-methy!pyridin-2 (ill) -one ; !-benzyl-4 - [ (4-methylben:yl) oxy] pyrzdin2 (IH) -one ; l-benzyl-4- (benzyloxy) -3,5-dibromo6-methylpyridin2 (IH) - one; 1-benzyl-4-(benzyloxy)-3,5-dibromo-6-methylpyridin-2(IH)- one; 3-bromo-l-(3-f!uorobenzyl)-4-(l-phenylethoxy)pyridin2 (iH)-one; 4- (benzyloxy) -i- [4- (trifluoromethyl) benzy!] pyridin-2 (IH) - one; 2-({ [3-bromo-2-oxo-l-(pyridin-3-ylmethyl)-l,2dihydropyridin-4-yl]oxy}methyl)-5-fluorobenzonitri!e; 5-bromo-4- [(2,4-difluorobenzyl)oxy]-l-(2,6difluorophenyl)-2-methyl-6-oxo-l,6-dihydropyridine-3carbonitrile; 4-(benzyloxy)-l-(3-fluorobenzyl)-3- (trifluoromethyl)pyridin-2(IH)-one; 3-bromo-4- [(2,4-difluorobenzyl)oxy]-l-(2,6difluorophenyl)-6-methyl-5-oxiran-2-ylpyridin-2(iH)-one; l-benzyl-4- [ (3-chlorobenzyl) oxy] pyridin-2 (IH) -one ; l-benzyl-4- [ (3-chlorobenzyl)oxy] pyridin-2 (IH) -one; 5-bromo-4-[ (2,4-difluorobenzyl) oxy] -I- (2,6difluorophenyl)-2-methyl-6-oxo-l,6-dihydropyridine-3carbaldehyde; tert-butyl 3- { [4- (benzyloxy) -3-bromo-2-oxopyridin-i (2H) - yl ] methyl } piperidine - 1 - carboxylate ; 3-bromo-4- [ (2,4-difluorobenzyl)oxy] -i- (2,6dif!uorophenyl) -6-methyl5-viny!pyridin2 (!H) -one; a- (benzy!oxy) - i- [4- (trifiuoromethcxv) benzyl ] pyridln2(IH) -one; 3-bromo-4- [(4-ch!orobenzy!)oxy]-l- [2- (phenyl hio) ethy! ] pyridin2 (IH) -one ; 3-Bromo-4- (4-chioro-benzyloxy) -I- {2-phenv-sulfanylethyl) - iH-pyridin-2-one ; 3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methvl-l- (2morpholin-4-ylethyl) pyridin-2 (IH) -one ; 4- [ (2,4-difluorobenzyl) oxy] -6- (hydroxymethy]) - !- (pyridin3-ylmethyl ) pyridin-2 (IH) -one ; 4- { [2- (Aminomethy!) -4fluorobenzyl] oxy} -3-bromo- !- (2,6dif!uorophenyl)-6-methylpyridin-2(iH)-one trifluoroacetate; 4- (benzyloxy) -i- (4fluorobenzyl) pyridln-2 (IH) -one; 4- (benzy!oxy) -i- (4fluorobenzyl) pyridin-2 (IH) -one; 4-Benzy!oxy-3-bromol-methanesul fonyl ~ IH-pyridin-2-one tert-butyl 4- [4- (benzyloxy)-3-bromo-2-oxopyridin-l(2H) yl] piperidine- !- carDoxylate ; !-benzyl-4- (benzyloxy) -3-vinylpyridin-2 (IH) -one; 4 - (benzyloxy) - 1 - [4 - (methyl thio) benzyl ] pyridin2 (IH) -one 3-Bromo-4- (2,4-difluoro-benzyloxy) - i- (2 -methyl -4methyl amino-pyrimidin5 - ylmethyl ) - IH-pyridin-2 -one ; 3 -bromo-4 - [ (2,4 -difluorobenzyl ) oxy] - 6 -methylpyridin2 (IH) -one ; l-benzyl-3-bromo-4- { [2- (trifluoromethyl) benzyl] oxy]pyridin2 (IH) -one ; l-benzyl-3-bromo-4- { [2- (trifluoromethyl) benzyl ] oxy}pyridin2 (1H) -one ; 4- [ (2,4-difluorobenzyl) oxy] -i- [5- (hydroxymethyl) -2- methylphenyl] -6-methylpyridin-2 (IH) -one; 4- (benzyloxy) -I- [4- (me hylsulfonyl) benzyl] pyridin-2 (IH) 4-Phenoxy-iH-pyridin-2-one; l-benzyl-4- [ (2-chlorobenzyl)oxy] pyr!din-2 (IH) -one; l-benzy!-4- [ (2-ch!oroben:yl) oxy] pyridin-2 (IH) -one ; methyl 4-{ [4- (benzy!oxy)-2-oxopyridin-l{2H) yl]methyl]benzoa=e; 4-[(2,4-dif!uoroben=yl)oxy]-l-(2,6-difluorophenyl)-6methy!pyridin-2(IH)-one; I- (3-f!uorobenzyl)-4-(pheny!ethyny!)pyridin-2(iH]-one; 4-(benzyloxy)-3-bromo-l-(piperidin-4-ylmethyl)pyridin- 2(IH)-one hydrochloride; 4-(benzyloxy)-3-bromo-l-(piperidin-4-ylmethyl)pyridin2(iH)-one hydrochloride; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-[2- (methylthio)pyrimidin-4-y!]pyridin-2(IH)-one; 4-(benzyloxy)-3-bromo-l-piperidin-4-ylpyridin-2(iH)-one hydrochloride; 4-Benzyloxy-l-difluoromethyl-IH-pyridin-2-one; 4-Benzyloxy-3-bromo-l-(2-chloro-phenyl)-6-methyl-iHpyridin-2-one; 3-Bromo-6-methyl-l-pyridin-3-ylmethyl-4-[(pyridin-3ylmethyl)-amino]-IH-pyridin-2-one; l-(3,4-Dichloro-benzyl)-6-oxo-l,6-dihydro-pyridine-3carboxylic acid (2,4-difluoro-phenyl)-amide; l-(2,6-Dimhloro-benzyl)-6-oxo-l,6-dihydro-pyridine-3- carboxylic acid (2,4-difluoro-phenyl)-amide; 5-Chloro-l-(2,6-dich!oro-benzyl)-6-oxo-l,6-dihydropyridine-3-carboxylic acid (2,4-difluoro-phenyl)-amide; 5-Chi 0 r 0-l-(2,6-dichl 0 r 0-benzyl)- 60 x 01, 6-dihydr 0pyridine-3-marboxylic acid methyl-phenyl-amide; l-(2,6-Dichloro-benzyl)-6-oxo-l,6-dihydro-pyridine-3carboxylic acid benzylamide; carboxylic acid (3-' =thy_am,no-p.o yl)-amide; (2,6-Dichloro-benzyl) 6-oxo 1,6 dl..< c-ov d_,.e J carbox¥lic acid (2-morpholin-_-y -e hy!)-amide; 4 N-[5-Acety!-l-(4-chloro-benzy!)-6-meth'fl-2-oxo-!,2dihydro-pyridin-3-yl]-4-ch!oro-benzamide; i-(2,6-Dichloro-benzyl)-6-oxo-i,6-dihydrc-pyridine-3carbox,/lic acid N'-(3-chloro-5-trifluoromethyl-mvrid n-2-yl - hydrazide; N-a!!yl-2-[(!-benzyl-6-oxo-!,6-dihydropyridin-3yl)carbonyl]hydrazinecarbothicamide; !-Benzyl-5-[5-(3,4-dichloro-benzylsulfanyl)- [l,3,4]oxadiazol-2-yl]-IH-pyridin-2-one; N'-{ [(l-benzyl-6-oxo-!,6-dihydropyridin-3yl)carbonyl]oxy}pyridine-4-carboximidamide; l-(2,6-Dichloro-benzyl)~6-oxo-l,6-dihydro-pyridine-3carboxy!ic acid 3-trif!uoromethyl-benzylamide; !-Benzyl-6-oxo-l,6-dihydro-pyridine-3-carboxylic acid (2morpholin-4-yl-ethyl)-amide; 5-[4-(3-Chloro-phenyl)-piperazine-l-carbonyl]-l-(3,4dichloro-benzyl)-iH-pyridin-2-one; 5-Chloro-l-(2,6-dichloro-benzyl)-6-oxo-l,6-dihydropyridine-3-carboxylic acid benzylamide; l-(4-Chloro-benzyl)-5-[3-(4-chloro-phenyl)- [l,2,4]oxadiazol-5-yl]-IH-pyridin-2-one; l-(4-Chloro-benzyl)-5-[3-(4-chloro-phenyl)- [l,2,4]oxadiazol-5-yl]-iH-pyridin-2-one; 2-Chloro-N-[l-(2,6-dichloro-benzyl)-6-oxo-5trifluoromethyl-l,6-dihydro-pyridin-3-yl]-4-fluoro-benzamide; N-[l-(2,6-Dichloro-benzyl)-6-oxo-5-trifluoromethyl-l,6dihydro-pyridin-3-yl]-4-isopropoxy-benzamidE; l-(2,6-Dichloro-benzyl)-6-oxo-l,6-dihydro-pyridine-3carboxylic acid (4~trifluoromethoxy-phenyl)-amide; carboxy!ic acid (3-trzfluoromethyl-phenyl)-amide; 5-Chloro-i-(2,6-dichloro-benzyl)-6-oxo-!,6-dihydropyridlne-3-carboxy!ic acid (3r.__uo_om tny=-phe.. = : • l V -, 1 -& i i_; = i-(2,6-Dichloro-benzyl)-6-oxo-l,6-dihydro-pyridine-3carboxylic acid (4-chloro-phenyl)-amide; !-(2,6-Dich!oro-benzyl)-6-oxo-!,6-dihydro-pyridine-3carboxy!ic acid (2-dimethy!amlno-ethyl)-amide; 5-Methy!-l-phenyl-!H-pyridin-2-one; 3-Bromo-l-(3-f!uoro-benzyl)-4-(3-methoxy-phenyl)-IHpyridin-2-one; 3-Bromo-l-(3-fluoro-benzyl)-4-(3-isopropyl-phenyl)-IHpyridin-2-one; 3,-Bromo-l'-(3-f!uoro-benzyl]-6-methoxy-l'H- [3,4']bipyridinyl-2'-one; 4-Benzo[l,3]dioxol-5-yl-3-bromo-!-(3-fluoro-benzyl)-iHpyridin-2-one; 3-Bromo-l-(3-fluoro-benzyl)-4-thiophen-3-yl-IH-pyridin-2one ; 3-Bromo-l-(3-fluoro-benzyl)-4-(3-trifluoromethyl-phenyl)- IH-pyridin-2-one; 3-Bromo-l-(3-fluoro-benzyl)-4-naphthalen-2-yl-iH-pyridin2-one; 3-Bromo-l-(3-fluoro-benzyl)-4-(4-fluoro-phenyl)-iH- pyridin-2-one; !-Benzenesulfonyl-4-benzyloxy-3-bromo-iH-pyridin-2-one; 4-[3-Amino-l-(2,4-difluoro-phenyl)-propoxy]-3-bromo-6methyl-l-pyridin-3-ylmethyl-iH-pyridin-2-one; l-(4-Bromo-2,6-difluoro-phenyl)-4-(2,4-difluoro- benzyloxy)-6-methyl-iH-pyridin-2-one; 2-[l-(4-Amino-2-methyl-pyrimidin-5-ylmethyl)-3-bromo-6methyl-2-oxo-l,2-dihydro-pyridin-4-yloxymethyl]-5-f!uorobenzonitrile; 4-(2,4-Difluoro-benzy!oxy)-6-methy!-l-(2,4,6-trif!uerophenyl)-iH-pyrid!n-2-one; !-(2-Chioro-4-hydroxy-phenyl)-4-(2,4-difluoro-benzyloxy)- 6-me n},l-!H-pyridin-2-one; 3-[4-(2,4-Difluoro-benzyloxy)-6-me hyl-2-oxo-2H-pyr dinl-yl]-benzcic acid methyl ester; 3-Bromo-!-(2,6-difluoro-phenyl)-4-methoxy-6-methv!-5viny!-iH-pyridin-2-one; 3-Bromo-!-(2,6-difluoro-phenyl]-4-methoxy-6-me hyi-5styryl-iH-pyridin-2-cne; l-(2,6-Difluoro-phenyl)-4-methoxy-6-methyl-5-phenethylIH-pyridin-2-one; 3-Bromo-l-(2,6-difluoro-phenyl)-4-methoxy-6-methyl-5- phenethyl-iH-pyridin-2-one; I- (iH-indazo!-5-yl)-4-(iH-indazol-5-ylamino)-6me hylpyridin-2(IH)-one; 5-Bromo-4-(2,4-difluoro-benzyloxy)-l-(2,6-difluorophenyl)-2- [2- (2,4-difiuoro-phenyl)-ethyl]-6-oxo-l,6-dihydro- pyridine-3-carbaldehyde; 4-[3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyridin-l-yl]-pyrimidine-2-carbonitrile; 3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2H- [l,2']bipyridinyl-5'-carboxylic acid; 3-Bromo-4-(5-carboxy-pyridin-2-yloxy)-6-methyl-2-oxo-2H- [l,2']bipyridinyl-5'-carboxylic acid; 3-Bromo-4-(2,4-difluoro-benzyloxy)-6,6'-dimethyl-2-oxo2H-[l,2']bipyridinyl-3'-carbonitrile; 3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2H- [l,2']bipyridinyl-5'-carboxylic acid methylamide; 3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2H- [l,2']bipyridinyl-5'-carboxylic acid (2-hydroxy-ethyl)-amide; [i, 2 '] bipyridinyl-5'-carboxylic acid (2-methoxy-ethyl)-amide; 3-BromoI- (2,6-difluoro-pheny!)-4-methoxy-6-me hyl-5-{4methyl-benzyl) - !H-Dvridin-2-one; 3-bromo-4- [(2 4-difluorobenzyl)oxy]-l-(2,6dif!uorophenyl) - 51,2-dihydroxy-2-phenylethyl)-6methylpyridin-2 (!H-one; 3-bromo-4- [ (2 4-difluorobenzyl)oxy]-5'-(l-hydroxy-!- methy!ethyl)-6-me hyi-2H-l,2'-bipyridin-2-one; 4-Benzyloxy-IH-pyridin-2-one; 4-Benzy!oxy-3-methyl-iH-pyridin-2-one; 2-Oxo-6-phenethyl-l,2-dihydro-pyridine-3-carbonitrile; 2-Oxo-6-phenyl-l,2-dihydro-pyridine-3-carbonitrile; 6-Oxo-l,6-dihydro-[2,3']bipyridinyl-5-carbonitri!e; 6-Oxo-l,6-dihydro-[2,3']bipyridinyl-5-carboxylic acid; 3-{ [4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- y!]methyl}benzamide; 3-bromo-4- [ (4-fluorobenzyl) oxy] -1- (4methoxybenzyl) pyridin-2 (IH) -one ; 3-bromo-4- [(4-fluorobenzyl)oxy]-l- (4met hoxybenzyl ) pyridin-2 (IH) -one ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -i- [2-fluoro-5- (hydroxymethyl)phenyl]-6-methylpyridin-2(iH)-one; 3-chloro-l-(4-fluorobenzyl)-4-[(4- fluorobenzyl) oxy] pyridin-2 (IH) -one; 3-chloroI- (4fluorobenzyl) -4- [ (4f luorobenzyl ) oxy] pyridin2 ( 1 H) - one ; 3-bromo-l-(3-chlorobenzyl)-4-[(4~ f!uorobenzyl)oxy]pyridin-2(IH)-one; 3-bromo-4-[(3,4-difluorobenzyl)oxy]-l-(3fluorobenzyl)pyridin-2(IH)-one; oxopyridin-l(2H)-y!]-4-methylbenzoic acid; 3-bromo-l- (3-chlorobenzvl)-4- [(4fluorobenzyi) oxy] pyridin-2 (IH) -one; 3-bromo-!- (3-chlorobenzyl)-4- [(4- f!uorobenzyl)oxy]pyridin-2(iH)-one; 4-{ [3-chloro-4- [(2,4-difluorobenzyl)amino]-6-methy!-2oxopvrldin-i(2H) -yl]methy!}benzonitrile trzfluoroacetate; 3 -bromo-4- [ (2,4-difluorobenzyl) oxy] - !- { [5- (I -hydroxymethyl ethyl) pyrazin2-yl] methyl } -6-methylpyridin2 (IH) -one 4- (benzyiamino) -3-bromo-l- (3-fluorobenzyl)pyrid'-n-2 (IH) one ; 4- (benzylamino) - 3-bromoi- (3fluorobenzyl) pyridin-2 (IH) one ; 2-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyi-2- oxopyridini (2H) -yl] methyl }benzonitrile ; 3-bromo-4- [ (2,4-difluorobenzyl)oxy] -I- [2-fluoro-6- (4methylpiperazin-l-yl)pheny!]-6-methy!pyridin-2 (IH)-one tri f !uoroacetate ; 4- [3-bromo-4- [ (2,4-difluorobenzy!)oxy] -6-methyl-2- oxopyridin1 (2H) -yl] -N-methylbenzamide ; I- [2- (aminomethyl) benzyl] -3-bromo-4- [(2,4di fluorobenzyl ) oxy] pyridin2 (IH) -one ; 3-bromo-l- (4-fluorobenzyl) -4- [ (4f luorobenzyl ) oxy] pyridin2 (IH) -one ; i- [2- (aminomethyl)benzyl] -3-bromo-4- [ (2,4di fluorobenzyl ) oxy] - 6 -methylpyridin2 (IH) -one ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [3- (piperidinl-ylcarbonyl) phenyl ] pyridin-2 (IH) -one ; l-benzyl-3-bromo-4- [ (4-chlorobenzyl) oxy] pyridin-2 (IH) one ; 4- [(2,4-difluorobenzyl)oxy]-l-(3-fluorobenzyl)-3methylpyridin-2 (IH) -one ; 4- (benzyloxy) - I- [4- (benzyloxy) benzyl ] -3-bromopyridin2 (1H) -one ; 4- [3-bromo-4- [(2,4-difluorobenzyl)oxyJ-6-methyl-2oxopyridin1 (2H) -vl ] -N-hydroxybenzamide ; 4 - (benzyloxy) -3 -bromo- !- [4 - (trif!uoromethyl) benzy! ] pyridin-2 (!H) -one ; 3-promo1 ~ (cyclopropylmethyl) -4- [ (4fluorobenzy!) oxy] pyridin-2 (IH) -one ; 3-bromo-l- (cyc!opropylmethyl)-4- [(4- fluorobenzyl)oxy]pyridin-2(iH)-one; l-benzyl-3-bromo-4- [ (3-ch!orobenzyl) oxy] -6-methylpyridin2 (IH)-one; l-benzy!-3-bromo-4- [ (3-chiorobenzyl) oxy] -6-methylpyridin2(iH)-one; l-benzyl-3-bromo-4- [ (3-chlorobenzyl) oxy] -6-methylpyridin2 (IH) -one; 2- { [3-bromo-4- [ (2,4-dif!uorobenzyl) oxy] -2-oxopyridin1 (2H) -yl] methyl }benzonitri!e; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- ({5- [ (methylamino) methyl] pyrazin-2-yl }methyl) pyridin-2 (IH) -one trifluoroacetate ; 3-bromo-l- (3fluorobenzyl) -4- [ (2methylbenzyl ) oxy] pyridin2 (IH) -one ; 3-bromoI- (3fluorobenzyl) -4- [ (2- methylbenzyl) oxy] pyridin-2 (IH) -one; methyl 3-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-2oxopyridin1 (2H) -yl] methyl }benzoate ; 3-bromoI- (3-fluorobenzyl) -6-methyl-4- (2phenylethyl) pyridin-2 (IH) -one ; 3-bromo-l- (3fluorobenzyl) -6-methyl-4- (2phenylethyl ) pyridin2 (IH) -one ; l-benzyl-3-bromo-4- [ (4-methylbenzyl) oxy] pyridin-2 (IH) - 4- (benzyloxy) -!- (3f!uorobenzy!) -3-iodopyridin-2 iH)-one; 3-bromo-4- [ (2,4-difluorobenzy!) oxy] - i- [3- (hydroxymethy!) phenyl ] - 6-methy!pyridin2 (IH) -one ; 4- (benzy!oxy) -i- (3f!uorobenzy!) - 3-iodopyr=din2 IH) -one; 3-{ [3-bromo-4- [(2,4-d=fluorobenzyl)oxy] -6-methvl-2oxopyridin-!(2H)-yl]methy!}benzoic acid; 3-bromo-4- [(4-fluorobenzyl)oxy]-l- [2- (hydroxymethy!) benzy! ] pyridin-2 (!H) -one; 3-bromo-4- [(2,4-difiuorobenzyl)oxy]-!- [ (5-{ [(2hydroxyethy!) (methyl) amino] methyl }pyrazin-2-yl) methyl] - 6methy!pyridin-2(IH)-one trifluoroacetate (salt) ; 4- (benzyloxy) - 3-bromoI- [ (6fluoropyridin-Byl)methyl]pyridin-2 (IH) -one; 3-bromo-4- [(4-chlorobenzyl)oxy]-l- (4f!uorobenzyl) pyridin-2 (IH) -one ; 3-bromo-4- [(4-chloro-2-f!uorobenzyl)amino]-l- (3f!uorobenzyl) pyridin-2 (!H) -one ; 4- (benzy!oxy) - 3-bromol-ethylpyridin2 (IH) -one ; 4- (benzyloxy) -3-bromo-l-ethylpyridin-2 (IH) -one; 4- (benzyloxy) -3-bromo-l-ethylpyridin-2 (IH) -one; 2- (2- { [3-bromo-4- [ (2, {-difluorobenzyl) oxy] -2-oxopyridini (2H) -yl ] methyl } phenyl ) acetamide ; 1 -benzyl - 3 -bromo4 - [ ( 2 - chl orobenzyl ) oxy] pyridin2 (IH) - one ; l-benzyl-3-bromo-4- [ (2-chlorobenzyl) oxy] pyridin-2 (IH) - one; methyl 2-{ [3-bromo-4- [(4-fluorobenzyl)oxy]-2-oxopyridin1 (2H) -yl] methyl }benzoate; 3-bromo-l- (2,6-dichlorophenyl) -4- [2- (4fluorophenyl) ethyl] - 6-methylpyridin-2 (IH) -one ; fluorophenyl)ethyl]-6-methylpyridin-2(iH)-one; 3-br 0 m 0-4-[(2,4-diflu 0 r 0 benzyl)oxy]-i-{5- [ isopropylamino)methyl]-2-methylpheny!}-6-methylpyridin2 !H)-one hydrochloride; 3-bromo-i- (3-fluorobenzyl)-4-(2-pheny!ethyl)pyriiln2 1H)-one; N_{3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methy!-2oxopyridin-l(2H)-yi]benzyl}-N'-methylurea; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-[3- (hydroxymethy!)phenyl]-6-methylpyridin-2(iH)-one; 3-bromo-l-(3-fluorobenzyl)-4-[(3f!uorobenzyl)oxy]pyridin-2(IH)-one; 4-(benzyloxy)-3-bromo-l-[2-(2-thienyl)ethyl]pyridin2 IH)-one; 4-(benzyloxy)-3-bromo-l-[2-(2-thienyl)ethyl]pyridin2 !H)-one; 3-bromo-4- [(2,4-difluorobenzyl)amino]-l- (2,6difluorophenyl) -6-methylp}'ridin-2 (!H) -one trifluoroacetate; 3-bromo-4- [ (2,4-difluorobenzyl)amino] -i- (2,6- difluorophenyl) -6-methylpyridin-2 (iH)-one trifluoroacetate; 3-bromo-4- [ (4-chlorobenzyl) oxy] -I- (4me t hoxybenzyl ) pyridin2 (IH) - one ; 3-bromo-4- [ (4-chlorobenzyl)oxy] -i- (4me thoxybenzyl ) pyridin2 (IH) - one ; 3-bromo-l- (4-chlorobenzyl) -4- [(4chlorobenzyl ) oxy] pyridin-2 (IH) -one ; 3-bromo-l- (3-fluorobenzyl)-4- [(4methoxybenzyl ) oxy] pyridin2 (IH) -one ; 3 - bromo1 - ( 3,5 - dibromo2,6 - di f i uoro4 - hydroxyphenyl ) - 4 [ (2,4-difluorobenzyl) oxy] -6-methylpyridin-2 (IH) -one; 4- (benzyloxy) -3-bromo-l- [4- (trlfluoromethoxy) benzyl] pyridin-2 (IH) -one; 4- (benzyloxy) -3-bromo-l- [4- (trifluoromethoxy) benzyl] pyridin-2 (-H) -one; N'-{3- [3-bromo-4- [(2,4-dif!uorobenzy!)oxy]-6-methyl-2oxopyridin1 (2H) -y! ] benzyl } -N, N-dimethylurea ; 3-bremo-4- [(4-f!uorobenzyl)oxy]-l- [4- (trifluoromethyl)benzyl]pyridin-2 (!H) -one; 2- { [3-bromo-4- [ (2,4-di fluorobenzyl) oxv] - 6-methyl2- oxopyridin1 (2H) -yl] methyl }benzamide; N-{3- [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2- oxopyridin1 (2H) -yl] benzyl }mormholine-4-carboxamide ; N- { 3 - [ 3 -bromo4 - [ ( 2,4 -di f luorobenzyl ) oxy] - 6 -methyl - 2 oxopyridin-1 (2H) -yl ] benzyl } methanesul fonamide ; 4- [3-bromo-4- [(2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin- ! (2H) -yl] -N-isopropylbenzamide ; 4- (a!lylamino)-3-bromo-l- (2,6-difluorophenyl)-5-iodo-6methylpyridin-2 (IH) -one ; 4-(allylamino)-3-bromo-l- (2,6-difluorophenyl)-5-iodo-6methylpyridin2 (IH) -one ; (4- { [4- (benzyloxy) -3-bromo-2-oxopyridin-i (2H) - yl]methyl}phenyl}acetic acid; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [4- ( pyrrol idin1 - yl carbonyl ) phenyl ] pyridi n2 (IH) - one ; l-benzyl -4 - (benzyloxy) - 3 - iodopyridin-2 (IH) -one ; I- (biphenyl-4-ylmethyl) -3-bromo-4- [ (4- f luorobenzyl ) oxy] pyridin2 (IH) - one ; 4- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin-l(2H)-yl]benzoic acid; 4- (benzyloxy) -3-promoi- [2- (3-thienyl) ethyl] pyridin2 (IH) -one; 4- (benzyloxy) -3-bromo-l- [2- (3-thienyl) ethyl] pyridin2 (!H)-one; 3-bromo-4- [ (4fluorobenzyl) oxy] - i- [3- (trifluoromethyl) benzyl] pyridin2 (IH) -one ; N- [3-bromo-l- (3fluorobenzy'-) -2-oxo-l, 2-dihydropyridin-4y! ] -4 - f luorobenzamide ; methyl 3- [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methy!-2- oxopyridin-i (2H)-yl]benzy!carbama%e; l-benzyl-4- (benzylthio) 3-bromopyridin-2 (iH)-one; 4- (benzyloxy) -3-bromoI- (4- "er[-butylbenzyl) pyridin2 (IH) -one; 4- (benzy!oxy) -3-bromo-l- (4tert-butylbenzyl) pyridin- 2 (iH)-one; N-{3- [3-bromo-4- [(2,4-difluorobenzy!)oxy]-6-methyl-2oxopyridin- ! (2H) -yl] benzyl } -2-methox-yacetamide ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] - I- ({ 5- [ (dimethyl amino) methyl ] pyrazin2 -yl } methyl ) - 6 - methylpyridin- 2 (IH)-one trifluoroacetate; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- [4- (piperazinl-ylcarbonyl) pheny!] pyridin-2 (!H) -one hydrochloride ; 4- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-2- oxopyridin1 (2H) -yl] -N,N-bis (2-hydroxyethyl) benzamide ; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -i- {5- [ (dimethyl amino) methyl ] - 2 -methylphenyl ] - 6 -methylpyridin2 (IH) - one hydrochloride ; 1 -benzyl - 3 -bromo4 - ( 2 -phenyl ethyl ) pyridin2 (IH) -one ; i- (3-fluorobenzyl) -4- [ (4fluorobenzyl) oxy] -3methylpyridin-2 (IH) -one ; 4 - (benzyloxy) -I - (piperidin-3 -ylmethyl ) pyridin-2 (IH) -one trifluoroacetate; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methylI- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-2 (IH) -one ; 4- (benzyloxy) I- (3-fluorobenzyl)-3-methylpyridin-2(IH)- oxopvrldin-l(2H)-yl]benzyl,gzY ".- - .... am.de hydrochloride; . 3-bromo-4- [(2,4-dif!uorobenzyl)oxv]-i- (2,6difluorophenv!) - 5-iodo-6-methy!pyridin-2 (IH) -one ; 3-bromo-4- [ (2,4-dif]uorobenzyl)oxy] -6-menhyi-i- [4- (piperidini-ylcarbony!) pheny!] pyrzdin2 (IH) -one ; N- [3-bromo-!- (3-f!uorobenzyl) -2-oxo-!,2-dihydropyrzdin-4yl] -2,6-difluoroDenzamide; 2- { [4- (benzyloxy) - 3-bromo-2-oxopyridzn- ! (2H} - y! ]mechyi } benzonitr'i!e ; 5-{ [3-bromo-4- [(2,4-dif!uorobenzyl)oxy] -6-methyl-2oxopyridin1 (2H) -y! ] methyl } -N-methylpyrazine-2-carboxamide 3-chloro-4- [(2,4-difluorobenzyl)amino]-l- (2,6difluorophenyl) - 6-methy!pyridin2 (IH) -one ; 3- [3-chloro-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-y!]benzoic acid; 3-bromo-l- (3-fluoroben=yl)-4- [(3fluorobenzyl) amino] pyridin-2 (IH) -one ; 3-bromo-l- (3-fluorobenzyl)-4- [(3- methoxybenzyl) oxy] pyridin-2 (IH) -one ; 3-bromo-l- (4tert-butylbenzyl) -4- [ (2,4difluorobenzyl) oxy] pyridin-2 (IH) -one ; N- { 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-2oxopyridin1 (2;4) -yl] benzyl } acetamide ; 2- ( {3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin-l(2H)-yl]benzyl}amino)-2-oxoethyl acetate; l-benzyI-4- (benzyloxy)-3-methylpyridin-2 (IH) -one; N- {3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl] benzyl }urea ; l-benzyl-4- (benzyloxy) -3-ethylpyridin-2 (IH) -one ; N- { 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-2oxopyridin-i (2H) -yl] benzyl } -2-hydroxyacetamide ; 3-bromo-4- [ (4-chlorobenzyl) oxy] -I- (2-phenylethyl) pyridine 2 (!H) -one ; 3-bromo-l-(3-chlorobenzyl)-4- [(4chlorobenzyl ) cxy] pyridin-2 {IH) -one ; I- [3- {aminomethy!)phenyl] -3-bromo-4- [(2,4difluorobenzyl) oxy] -6-methylpyridin-2 (IH) -one ; 2 - { [4- (benzyloxy) - 3 -bromo2-oxopyridin1 (2H) - yl ] meLhyl }benzamide ; !- (4-fiuorobenzyl)-4- [(4-fluorobenzyl)oxy]pyridin-2 (IH) one ; I- [2- (aminomethyl)benzyl] -4- (benzyloxy) -3-bromopyridin2 (IH) -one; methyl 3- [4- (benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl ] propanoaLe; l-benzyl-4- (benzy!oxy) -3-methylpyridin-2 (IH) -one ; 4- (allylamino)-l- (2,6-dif!uorophenyl)-5-iodo-6methylpyridin-2 (IH) -one ; 4- (al!ylamino) -I- (2,6-difluorophenyl) -5-iodo-6methy!pyridin-2 (!H) -one ; 3 -bromo1 - ( 3 - f luorobenzyl ) -4 - (phenylethynyl) pyridin2(IH)-one; 4- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl ] -N, Ndimethylbenzamide ; { 4 - [ ( { 4 - (benzyloxy) - 3 -bromoI- [4 - (carboxymethyl) benzyl] 1,2-dihydropyridin-2-yl}oxy) methyl]phenyl}acetic acid; 4- (benzyloxy) -3-bromo-l- [3- ( tri f luoromethyl ) benzyl ] pyridin2 (IH) ~ one ; 4- (benzyloxy) -3-ethynyl-l- (3fluorobenzyl) pyridin-2 (IH) one; 3-bromo-4- [(2,4-difluorobenzyl)oxy]-l-{3- [ (dimethylamino) methyl] phenyl } - 6 -methylpyridin2 (IH) -one ; 4 - (benzyloxy) -3-bromol-methylpyridin2 (IH) -one ; !-benzyl-3-bromo-4- (phenylethynyl) pyridin-2 (IH) -one ; 4- (benzy!oxy) - 3-bromo- !-methy!pyridin-2 (!H) -one ; 3-bromo-l- (3-fluerobenzyl) -4- [ [4- ([rifluorome hyl) benzyl] oxy}pyridin-2 (IH) -one; 4- (benzyiamino) -3-bromo-i- (2,6-dif!uorcphenyi)-5-!odo-6methylpyrldin-2 (!H) -one ; 4- [ (2,4-difluorobenzy!) oxy] - !- (4-methoxybenzy!) - 6methyipyridin-2 (IH) -one ; 4- (benzyloxy) - 3-bromol-methyipyridin2 (ill) -one hydrobromide; 4- (benzyloxy) -3-bromo-!- [4- (morpho!in-4ylcarbonyl ) phenyl ] pyridin-2 (IH) -one; 5-bromo-4- [ (2,4-difluorobenzyl)oxy]-!- (2,6difluorophenyl)-6-oxo-!,6-dihydropyridine-2-carboxylic acid; l-benzyl-3-bromo-4- [ (2,6-dichlorobenzyl) oxy] pyridin2 (IH)-one; 3- [3-chloro-4- [(2,4-dlfluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-2-methylbenzoic acid; 4- [4- (benzyloxy) -3-bromo-2-oxopyridin1 (2H) _yl] benzoic acid; ethyl N- (5-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6me thyl - 2 - oxopyridin1 (2H) - yl ] methyl } - 2 - met hyl pyrimidin4 - yl)glycinate trifluoroacetate; 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -I- (2,6- difluorophenyl) -6-methyl-5- [ (E) -2-phenylvinyl] pyridin-2 (IH) one ; 3-bromo-l- (3fluorobenzyl) -4- { [3- ( tri fluoromethyl ) benzyl ] amino } pyridin2 (IH) - one ; 3-bromo-4- [ (4fluorobenzyl) oxy] -i- (3- phenylpropyl) pyridin-2 (IH) -one; 3-bromo-1- (4tert-butylbenzyl) -4- [ (4fluorobenzyl) oxy] pyridin-2 (IH) -one; methylpyridin-2 (IH) -one; l-cyc!ohexyl-4- [ (2,4-difluorobenzyl) oxy] -3,6cizmethy!pyridin-2 (!H) -one ; 3-bromo-4- [(2,4-difluorobenzyl)oxy]-l- (2,6difluorophenv!) - 5- (hydroxy ethyl) -6-methylpyrldin-2 (iH) -one ; l-benzy!-4- (benzyioxy) -2-oxoI, 2-dihydropyrzdine3- carbaldehyde ; 4- [ (2,4-difluorobenzyl) oxy] -6 -methyll-prop2-yn- !- ylpyridin-2 (IH) -one ; e hyl 3- [4- (benzyloxy)-3-bromo-2-oxopyridln-l(2H) - yl ] propanoate ; -benzyl-4- (benzyloxy)-3-(hydroxymethyl pyridin-2(!H)- one ; or a pharmaceutically acceptable salt thereof. 3-Chioro-4-(2,4-difluoro-benzyioxy)-6-methyl-l-(5-methy!- pyrazin-2-ylmethyl)-iH-pyridin-2-one 3-Chloro-4-(2,4-difluoro-benzyloxy)-l-(5-hydroxymethylpyrazin-2-ylmethyl)-6-methyl-iH-pyridin-2-one 3-Bromo-4-(2,4-dif!uoro-benzy!oxy)-l-(2,3-dihydro-iHindol-5-ylmethyl)-lH-pyridin-2-one 3-Bromo-4-(2,4-difluoro-benzyloxy)-l-[l-(2-hydroxyacetyl)-2,3-dihydro-IH-indol-5-ylmethyl]-6-methyl-iH-pyridin2-one 3-Bromo-4-(2,4-difluoro-benzyloxy)-6-methyl-l-(iHpyrazol-3-ylmethyl)-iH-pyridin-2-one 3-[3-Chloro-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyridin-l-yl]-4,N-dimethyl-benzamide 3-[3-Chloro-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2H- pyridin-l-yl]-4-methyl-benzamide 3-[3-Chloro-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo-2Hpyridin-l-yl]-4-fluoro-N-methyl-benzamide 2-oxo-2H-pyridin-l-y!]-N-methyl-benzamide 3-[3-Chloro-4- (9 _, 4-dif!uoro-benzv!oxy)-" -. =- ": ....... _-2-cxo-ZHpyridin-!-yl]-4-fluoro-benzamide 4- [3-Chloro-4-(2,4-difiuoro-benzp'loxyl,-6-meth\'!-S-cxo-2Hpy .... n-l-yl]-3,N-dimethyl-benzamide 3-Chloro-4-(2o4-difluoro-benzy!oxy)-!-[4-(!,2-dih}'drox}- ethyl)-2-methyl-phenyl]-6-methyl-iH-pyridin-2-one N-{4-[3-Ch!oro-4-(2,4-difluoro-benzy!oxy)-6-meth}'i-2-oxo- 2H-pyridin-!-yimethy!]-pheny!}-2-hydroxy-acetamide l-Hydroxy-cyc!opropanecarboxylic acid 4-[3-chloro-4-(2,4difluoro-benzyloxy)-6-methyl-2-oxo-2H-pyridin-l-y!methyl]- benzylamide N-{4-[3-Chloro-4-(2,4-difluoro-benzyloxy)-6-methyl-2-oxo- 2H-pyridin-l-ylmethyl]-benzyl}-2-hydroxy-acetamide N-{4-[3-Chloro-4-(2,4-dif!uoro-benzylox},)-6-methyl-2-oxo2H-pyridin-l-ylmethyl]-phenyl}-acetamide {2-[3-Bromo-l-(2,6-dif!uoro-phenyl)-6-methyl-2-oxo-l,2dihydro-pyridin-4-yloxymethyl]-5-fluoro-benzyl}-carbamic acid ethyl ester The above names were generated using ChemDraw Ultra version 6.0.2, which is put out by CambridgeSoft.com, Cambridge, MA; or ACD Namepro version 5.09, which is put out by ACDlabs.com. Definitions As used herein, the term "alkenyl" refers to a straight or branched hydrocarbon of a designed number of carbon atoms containing at least one carbon-carbon double bond. Examples of alkenyl" include vinyl, allyl, and 2-methyl-3-heptene. The term "alkoxy" represents an alkyl attached to the parent molecular moiety through an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy and isopropoxy. The term "thioalkoxy" represents an alky! attached to the parent molecular moiety through a sulfur atom. Examples of thioa!koxy groups include, for example, thiomethoxy, thioethoxy, thiopropoxy and thioisopropoxy. As used herein, the term "alkyl" includes those alkv! groups of a designed number of carbon atoms. A!kyl groups may be straight or branched. Examples of "alkyl" include methyl, ethyl, propyl, isopropyl, butyl, iso-, secand tert-butyl, pentyl, hexyl, heptyl, 3-ethylbuty!, and the like. "Cx-Cy aikyl" represents an alkyl group of the specified number of carbons. For example, CI-C 4 alkyl includes all aikyl groups that include at least one and no more than four carbon atoms. it also contains subgroups, such as, for example, C 2 -Cj alkyl or C:-C 3 alkyl. The term "aryl" refers to an aromatic hydrocarbon ring system containing at least one aromatic ring. The aromatic ring may optionally be fused or otherwise attached to other aromatic hydrocarbon rings or non-aromatic hydrocarbon rings. Examples of aryl groups include, for example, phenyl, naphthyl, 1,2,3,4-tetrahydronaphthalene, indanyl, and biphenyl. Preferred examples of aryl groups include phenyl and naphthyl. The most preferred aryl group is phenyl. The aryl groups herein are unsubstituted or, as speciied, substituted in one or more substitutable positions with various groups. Thus, such aryl groups can be optionally substituted with groups such as, for example, C -C 6 alkyl, CI-C alkoxy, halogen, hydroxy, cyano, nitro, amino, monoor di-(Ci- C 6 }alkylamino, C 2 -C alkenyl, C 2 -C 6 alkynyl, CI-C 6 haloalk-yl, CI-C haloalkoxy, amino(Ci-C )alkyl, monoor di(Ci-C 6 )alkylamino(C 1 - The term "arylalkyi" refers to an ary! group, as defined above, attached to the parent molecular moiety :hrough an aikyl group, as defined above. Preferred arvlalkv! groups include, benzyl, phene-hy!, phenpropy!, and ohe bu[\i. More preferred arylalkyl groups include ben-yl and zhene=hv!. The most preferred aryla!kyl group is benzyl. The aryl portions of %hose groups are unsubstituted or, as specifled, substituted in one or more substitutable positions wi-h various groups. Thus, such aryl groups can be optionai!y substituted with groups such as, for example, C -C 6 a!ky!, C -C aikoxy, halogen, hydroxy, cyano, nitro, amino, monoor di- (C-- C 6)alkylamino, C 2 -C 6 alkeny!, C 2 -C alkynyl, C 1 -C 6 haloalkyl, CI-C 6 haioalkoxy, amino(C- -C )alky!, monoor di(C:-C 6 )a!kylamino(C 1 - C ) alkyl. The term "ary!a!koxy" refers to an aryl group, as defined above, attached to the parent molecular moiety through an alkoxy group, as defined above. Preferred arylaloxy groups include, benzyloxy, phenethyloxy, phenpropyloxy, and phenbucyloxy. The most preferred arylalkoxy group is benzyloxy. The term"cycloalkyl" refers to a C]-C 8 cyclic hydrocarbon. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexy!, cycloheptyl and cyclooctyl. More preferred cycloalkyl groups include cyclopropyl. The term "cycloalkylalkyl," as used herein, refers to a C 3-C 8 cycloalkyl group attached to the parent molecular moiety through an alkyl group, as defined above. Examples of cycloalkylalkyl groups include cyclopropylmethyl and cyclopentylethyl. The terms "halogen" or "halo" indicate fluorine, chlorine, bromine, or iodine. The term "heterocyc!oalkyl," refers to a non-aromatic ring system containing at least one heteroatom selected from nitrogen, oxygen, and sulfur, wherein =he non-aromatic heterocycle is attached to the core. ?he he erocycloalkyl ring may be optionally fused to or otherwise atSached to o%her heterocycloalkyl rings, aromatic heterocycles, aroma=ic hydrocarbons and/or non-aromatic hydrocarbon rings. Preferred heterocyc!oalkyl groups have from 3 to 7 members. Examples of heterocycloalkyl groups include, for example, piperazzne, !,2,3,4-tetrahydroisoquinoline, morpholine, piperidine, tetrahydrofuran, pyrrolidine, and pyrazole. Preferred heterocycloalkyl groups include piperidinyl, piperazinyl, morpholinyl, and pyrolidinyl. The heterocycloalkyl groups herein are unsubstituted or, as specified, substituted in one or more substitutable positions with various groups. Thus, such heterocycloalk¥1 groups can be optionally substituted with groups such as, for example, CI-C 6 alkyl, CI-C 6 alkoxy, halogen, hydroxy, cyano, nitro, amino, monoor di-(C 1 - C 6)alkylamino, C 2 -CGalkenyl, C 2 -C 6 alkynyl, CI-C 6 haloalkyl, CI-C haloalkoxy, amino(Ci-C 6 )alkyl, monoor di(Ci-C )alkylamino(C 1 - CG) alkyl. The term "heteroaryl" refers to an aromatic ring system containing a least one heteroatom selected from nitrogen, oxygen, and sulfur. The heteroaryl ring may be fused or otherwise attached to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings or heterocycloalkyl rings. Examples of heteroaryl groups include, for example, pyridine, furan, thiophene, 5,6,7,8-tetrahydroisoquinoline and pyrimidine. Preferred examples of heteroaryl groups include thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl, benzimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isoxazolyl, oxadiazolyl, isothiazolyl, benzisothiazolyl, triazolyl, tetrazolyl, pyrroly!, indoly!, pyr£zolyl, and benzopyrazo!yl. Preferred he=eroal-/l groups include pyridy!. The heteroaryl roups herein are unsubstituted or, as sDecif ....{= , subsoil-''J ec in one or more substitu[ab!e_Positions with various, c o ?=._ Thus, such hezeroary! groups can be optionally subszi=u=ed with groups such as, for example, CI-C alky!, C 1 -C alkoxy, halogen, hydroxy, cyano, hi=to, amino, monoor di-(C 1 -C 6 ) inflammatory :- C 2-C alkenyl, C 2 -C alkynyl, C:-C 6 haloa!kyl, C -C haloalkoxy, amino(C -C )alkyl, monoor di(C -C )alkylamino(C -C )alky!. The term "he5eroarylalkyl" refers to a heteroaryl group, as defined above, attached to the parent molecular moiety through an a!kyl group, as defined above. Preferred heteroary!alkyl groups include, pyrazolemethyl, pyrazo!eethyl, pyridylmethyl, pyridy!ethyl, thiazolemethyl, thiazoleethyl, imidazo!emethyl, imidazo!eethy!, thienylmethyl, thienylethyl, furanylmethyl, furanyle:hyl, isoxazolemethyl, isoxazoleethyl, pyrazinemethyl and pyrazineethyl. More preferred heteroarylalkyl groups include pyridylmethyl and pyridylethyl. The heteroary! portions of these groups are unsubstituted or, as specified, substituted in one or more substitutable positions with various groups. Thus, such heteroaryl groups can be optionally substituted with groups such as, for example, CI-C alkyl, C -CG alkoxy, halogen, hydroxy, cyano, nitro, amino, monoor di- (Ci-C 6 )alkylamino, C 2 -C 6 alkenyl, C 2 - C 6 alkynyl, CI-C 6 haloalkyl, CI-C haloalkoxy, amino(Ci-C 6 )alkyl, monoor di(Ci-C 6 )alkylamino(Ci-C 6 )alkyl. If two or more of the same substituents are on a common atom, e.g., di(Ci-C )alkylamino, it is understood that the nature of each group is independent of the other. As used herein, the term "p38 mediated disorder" refers to any and all disorders and disease states in which p38 plays a role, either by control of p38 itself, or by p38 causing another factor to be released, such as but not limited to ILI, IL-6 or IL-8. A disease state in which, for instance, IL-! is a major component, and whose production or action, is exacerbated or secreted in response to p38, would therefore be considered a disorder mediated by p38. As TNF-beza has close structural homology with TNF-a!pha (a!so known as cachectin), and since each induces similar biologic responses and binds to the same cellular receptor, the synthesis of both TNF-alpha and TNF-beta are inhibited by the compounds of the present invention and thus are herein referred to collectively as "TNF" unless specifically delineated otherwise. Non-toxic pharmaceutically acceptable salts include, but are not limited to salts of inorganic acids such as hydrochloric, sulfuric, phosphoric, diphosphoric, hydrobromic, and nitric or salts of organic acids such as formic, citric, malic, maleic, fumaric, tartaric, succinic, acetic, lactic, methanesulfonic, p-toluenesulfonic, 2-hydroxyethylsu!fonic, salicylic and stearic. Similarly, pharmaceutically acceptable cations include, but are not limited to sodium, potassium, calcium, aluminum, lithium and ammonium. Those skilled in the art will recognize a wide variety of non-toxic pharmaceutically acceptable addition salts. The compounds of this invention may contain one or more asymmetric carbon atoms, so that the compounds can exist in different stereoisomeric forms. These compounds can be, for example, racemates, chiral non-racemic or diastereomers. In these situations, the single enantiomers, i.e., optically active forms, can be obtained by asymmetric synthesis or by resolution of the racemates. Resolution of the racemates can be accomplished, for example, by conventional methods such as crystallization in the presence of a resolving agent; chromatography, using, for example a chiral HPLC column; or derivatizing the racemic mixture with a resolving reagent to generate diastereomers, separating the d =s ereomers vla chromatography or s ecu_v = " = crystallization, and removing the resolving agent to generate she origina! compound in enantiomerica!!y enriched form. Any of the above procedures can be reoeated to increase the enantiomeric purity of a compound. The compounds of the invention may exist as atropisomers, i.e., chiral rotational isomers. The invention encompasses the racemic and the resolved atropisomers. The following illustration generically shows a compound (Z) that can exist as azropisomers as well as its two possible atropisomers (A) and (B). This i!lustration also shows each of atropisomers (A) and (B) in a Fischer projection. In this illustration, R 1 , R 2 , and R 4 carry the same definitions as set forth for Formula I, Rp, is a substituent within the definition of Rs, and Rp is a non-hydrooen substituent within the definition of Rs. When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry., and unless otherwise specified, it is intended that the compounds include the cis, trans, Zand Econfab_gu_a lons. Likewise, all tautomeric forms are also intended to be 5ncluded. The compounds of general Formula E may be administered orally, topically, parentera!ly, by inhalation or spray or rectally in dosage unit formulations containing conventional non-toxlc pharmaceutically acceptable carriers, adjuvants and veh&c!es. The term parenteral as used herein includes percutaneous, subcutaneous, intravascular (e.g., intravenous), intramuscular, or intrathecal injection or infusion techniques and the like. In addition, there is provided a pharmaceutical formulation comprising a compound of general Formula I and a pharmaceutically acceptable carrier. One or more compounds of general Formula I may be present in association with one or more non-toxic pharmaceutically acceptable carriers and/or diluents and/or adjuvants, and if desired other active ingredients. The pharmaceutical compositions containing compounds of general Formula I may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsion, hard or soft capsules, or syrups or elixirs. For oral administration, the pharmaceutical composition may be in the form of, for example, a tablet, hard or soft capsule, lozenges, dispensable powders, suspension, or liquid. The pharmaceutical composition is preferably made in the form of a dosage unit containing a particular amount of the active ingredient. Examples of such dosage units are tablets or capsules. Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents selected from the group consisnlng of sweetening agents, __avo__ng =] agents, coloring agents and preservative agents in order to provide pharmaceutically e!eganz and palatable preparations. Tablets contain the actor= ingredient admixture with non-toxic pharma:eut a Ly acceptable excimients thaE are suitable for the manu=acture ef tablets. These recipient may be o_ = example inert diluenns, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, ge!atin or acacia, and lubricating agents, for example magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by known techniques. In some cases such coatings may be prepared by known techniques to delay disintegration and absorption in the gastro:ntesZina! tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monosterate or glyceryl distearate may be employed. Formulations for oral use may also be presented as hard gelatin capsules, wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate, or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin or olive oil. Formulations for oral use may also be presented as lozenges. Aqueous suspensions contain the active materials in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydropropyl-methylceilu!ose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents may be a naturally-occurring phosphatide, for example, lecithin, or condensation products of an alky!ene oxide with fatty acids, for example polyoxye%hylene stearate, or condensation products of echyiene oxide with long chain aliphatic alcohols, for example heDtadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monoo!eate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions may also contain one or more preservatives, for example ethyl, or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose or saccharin. Oily suspensions may be formulated by suspending the active ingredients in a vegetable oil, for example arachis oil, olive oi!, sesame oil, or coconut oil, or in a mineral oil such as liquid paraffin. The oily suspensions may contain a thickening agent, for example beeswax, hard paraffin, or cetyl alcohol. Sweetening agents and flavoring agents may be added to provide palatable oral preparations. These compositions may be preserved by the addition of an antioxidant such as ascorbic acid. Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents or suspending agents are exemplified by those already mentioned above. Additional excipients, for example sweetening, flavoring, and coloring agents, may also be present. Pharmaceutical compositions of the invention may a!so be in the form of oil-in-water emulsions. The oily phase may be a vegetable oil or a mineral oil or mixtures of these. Suitable emulsifying agents may be natura!iy-occurrin= =ums, for example gum acacia or um tragacanch, n=.ura,l}- .... _-, phosphatides, for example soy bean, lecithin, and esters or part_a esters derived from fatty acids and hexi- anhydrides, for example sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethyiene sorbitan monooleate. The emulsions may also contain sweetening and flavoring agents. Syrups and elixirs may be formulated with sweetening agents, for example glycerol, propy!ene glycol, sorbitol, glucose or sucrose. Such formulations may also contain a demulcent, a preservative, and flavoring and coloring agents. The pharmaceutical compositions may be in the =orm of a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents that have been mentioned above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parentally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic monoor diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. The compounds of general Formula I may also be administered in the form of suppositories, e.g., for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient that is solid at ordinary temperatures but li uid at the recta! temperature and will therefore me!t in the rectum to release the drug. Such materials include cocoa butter and polyethylene glycols. Compounds of general Formula I may be administered parentera!l Z in a sterile medium. The drug, depending on the vehicle and concentration used, can either be suspended or dissolved in the vehicle. Advantageously, adjuvants such as local anesthetics, prese vatives, and buffering agents can be dissolved in the vehicle. The active ingredient may also be administered by injection (IV, IM, subcutaneous or jet) as a composition wherein, for example, saline, dextrose, or water may be used as a suitable carrier. The pH of the composition may be adjusted, if necessary, with suitable acid, base, or buffer. Suitable bulking, dispersing, wetting or suspending agents, including mannitol and PEG 400, may also be included in the composition. A suitable parenteral composition can also include a compound formulated as a sterile solid substance, including lyophilized powder, in injection vials. Aqueous solution can be added to dissolve the compound prior to injection. For disorders of the eye or other external tissues, e.g., mouth and skin, the formulations are preferably applied as a topical gel, spray, ointment or cream, or as a suppository, containing the active ingredients in a total amount of, for example, 0.075 to 30% w/w, preferably 0.2 to 20% w/w and most preferably 0.4 to 15% w/w. When formulated in an ointment, the active ingredients may be employed with either paraffinic or a water-miscible ointment base. Alternatively, the active ingredients may be formulated in a cream with an oil-in-water cream base. If desired, the aqueous phase of the cream base may include, for example at least 30% w/w of a polyhydric alcohol such as propyiene glycol, butane-l,3-di , mannzto!, sorbi ol, glycerol, polyethylene glycol and mixtures thereof. The toazcai stimulation may desirably include a compound, which enhances absorption or penetration of nhe active ingredient [hrouch zhe skin or other affected areas. Examples of such dermal penetration enhancers include dimethylsulfoxide and related analogs. The compounds of this invention can also be administered by a transderma! device. Preferably topical adminis razion will be accomplished using a patch either of the reservoir and porous membrane type or of a solid matrix variety. In either case, the active agent is delivered continuously from the reservoir or microcapsules through a membrane into the active agent permeable adhesive, which is in contact with the skin or mucosa of the recipient. If the active agent is absorbed through the skin, a controlled and predetermined flow of the active agent is administered to the recipient, in the case of microcapsules, the encapsulating agent may also function as the membrane. The transdermal patch may include the compound in a suitable solvent system with an adhesive system, such as an acrylic emulsion, and a polyester patch. The oily phase of the emulsions of this invention may be constituted from known ingredients in a known manner. While the phase may comprise merely an emulsifier, it may comprise a mixture of at least one emulsifier with a fat or oil or with both a fat and an oil. Preferably, a hydrophilic emulsifier is included together with a lipophilic emulsifier, which acts as a stabilizer. It is also preferred to include both an oil and a fat. Together, the emulsifier(s) with or without stabilizer(s) make-up the so-called emulsifying wax, and the wax together with the oil and fat make up the socalled emulsifying ointment base, which forms the oily, dispersed phase of the cream formulations. Emulsifiers and emulsion stabilizers suitable for use in the formulatron of the present invention include Tween 60, Span 80, ceCostearyi alcoho!, myristyl alcohol, glyceryl monostearate, and sodium !auryl sulfate, among others. The choice of suitable oi!s or fats for the formulation is based on achieving the desired cosmetic properties, since the solubility of the active compound in most oils likely to be used in pharmaceutical emulsion formulations is very low. Thus, the cream should preferably be a non-greasy, non-staining and washable product with suitable consistency to avoid leakage from tubes or other containers. Straight or branched chain, monoor dibasic alkyl esters such as di-isoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2ethylhexyl palmitate or a blend of branched chain esters may be used. These may be used alone or in combination depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and/or liquid paraffin or other mineral oils can be used. Formulations suitable for topical administration to the eye also include eye drops wherein the active ingredients are dissolved or suspended in suitable carrier, especially an aqueous solvent for the active ingredients. The anti- inflammatory active ingredients are preferably present in such formulations in a concentration of 0.5 to 20%, advantageously 0.5 to 10% and particularly about 1.5% w/w. For therapeutic purposes, the active compounds of this combination invention are ordinarily combined with one or more adjuvants appropriate to the indicated route of administration. If administered per os, the compounds may be admixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate, polyvinyipvrro!idone,, and/or poi\n:lnvl. . =- o..o_' - s, and = ...... tableted or encapsulated for cony - clone ....... t administration. Such capsules or t- = ..... s may contain a control!ed-re!ease formulation as may be provided in a dispersion of active compound in hydrox? ropylmethy! cellulose. Formu!aticns for parentera! administration may be in the form of aqueous or non-acrueous isotonic sterile injection solutions or suspensions. These solutions and suspensions may be prepared from sterile powders or granules having one or more of the carriers or di!uents mentioned for use in the formulations for oral administration. The compounds may be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and/or various buffers. Other adjuvants and modes of administration are well and widely known in the pharmaceutical art. The amount of therapeutically active compounds that are administered and the dosage regimen for treating a disease condition with the compounds and/or compositions of this invention depends on a variety of factors, including the age, weight, sex and medical condition of the subject, the severity of the inflammation or inflammation related disorder, the route and frequency of administration, and the particular compound employed, and thus may vary widely. The pharmaceutical compositions may contain active ingredients in the range of about 0.I to I000 mg, preferably in the range of about 7.0 to 350 mg. A daily dose of about 0.01 to I00 mg/kg body weight, preferably between about 0.i and about 50 mg/kg body weight and most preferably between about 0.5 to 30 mg/kg body weight, may be appropriate. The daily dose can be administered in one to four doses per day. In the case of skin conditions, it may be preferable to apply a topical preparation of compounds of this invention to the affected area two to four times a day. It wil! be understood, however, that the specific dose leve! for any particular patient wil! depend upon a variety of factors including the activity of the specific compound emp!oyed, the age, body weight, general health, sex, diet, time of administration, route of administration, and rate of excretion, drug combination and the severity of the particular disease undergoing therapy. For administration to non-human animals, the composition may also be added to the animal feed or drinking water. It may be convenient to formulate the animal feed and drinking water compositions so that the animal takes in a therapeutically appropriate quantity of the composition along with its diet. It may also be convenient to present the composition as a premix for addition to the feed or drinking water. The disclosures in this application of all articles and references, including patents, are incorporated herein by reference. The invention is illustrated further by the following examples, which are not to be construed as limiting the invention in scope or spirit to the specific procedures described in them. The starting materials and various intermediates may be obtained from commercial sources, prepared from commercially available compounds, or prepared using well-known synthetic methods. The compound names in this application were created using ACD Name Pro version 5.09, or ChemDraw ultra version 6.0.2, software. Genera! Synthetic Procedures Remresentanive. p. oc -=_s for the .preparation. of compounds of the invention are outline below in the Schemes The star=ing materials can be purchased or ..... .... a_ea " using methods known to those skilled in the at=. Sim=iarly, the _D- = -- c__=__on o = the various intermediates can be achieved u=,. '-=- methods known in t = art. The s ..... ng manerlals may be varied and additional stems employed to produce compounds encompassed by the invention, as demonstrated by the examples below. In addition, different solvents and reagents can typically be used to achieve he above transformations. Protection of reactive groups may also be necessary to achieve the above transformations. In general, the need for protecting groups, as well as the conditions necessary to attach and remove such groups, will be apparent to those skilled in the art of organic synthesis. When a protecting group is employed, deprotection will generally be required. Suitable protecting groups and methodology for protection and deprotection such as those described in Protecting Groups in Organic Synthesis by Greene and Wuts are known and appreciated NO 2 CI Scheme 1 OBn B n O..v.--' 'i ', i I , ,,NH Hal NH o O (i) (ii) (iii) (iv)(v) Z = alkyl, aryl, arylalkyl, hydrogen, Hal = halogen heteroarylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroaryl, heterocycloalkyl, -C(O)NH(CH 2)naryl, -C(O)N(alkyl)(C H 2 )naryl, BnO N Hal" N'Rs Hal II "R O O O (viii) (vii) (vi) In Lhis scheme, Rs is as defined above. Alternatively, the compounds of the instant invention can be prepared according to the method outlined in Scheme 2. Scheme 2 R 2 OH NH 2 ; @ 0 CH 3 (Q). (ix) (x) (xi) In Scheme 2, Q at each occurrence is independently alkyl, halogen, alkoxy, arylalkoxy, thioalkoxy, alkoxycarbonyl, arylalkoxycarbonyl, CO 2 H, CN, amidinooxime, NR RT, NR 6 R alkyl, -C(O)NR 6 R amidino, haloalkyl, or haloalkoxy; and n is 0, I, Alternatively, Compounds. using the procedures the X, X', R, R' and aryl, her eroa.y=, " amine, described above for of the i ..v_n { - ..... can be prepared outlined =n Schemes 3-25. in Schemes 3- R'' substituen:s en croups such as and alkyl, carry the same aerlnlt:on ..... substizuents on these groups. Scheme 3 HO .x R 4 NH,OH HOx R 4 Rk /X R'V O R O /NH Base x]f-NH II O O O NCS, dichloroacetic acid Dichloroethane/Acetic Acid (2:1 v/v) "C. 4,5/ Br 2, HOAc R O R4 CI/ NH O Scheme 4 1) RAoH R" 7 Base H Scheme Br R s11-6 Base N X Br R / 1'1"6 Base// NBS or Br 2 or NCS or CI 2 Scheme 6 NBS or Br 2 or NCS or CI 2 HOo X X R' Base NBS or Br 2 or NCS or Cl 2 Scheme 7 DMF/DIAD (1.1 OH pPh 3 (resisn) 1 / x -10° C 20 min R 4 RANDOM R"OH (1.2eq) -10° C 30 min, R PPh 3 resisn 3 mmol=! Scheme (CF 3 SO 2) 2 0 R i, Et 3 N, CH 2 CI 2 O R 4 I - 30 °C Rs PtO 2 H 2 , 10 psi min, RT EtOAc/EtOH Scheme Scheme NH 2 R,...J" O/ -. IL o-dichlorobenzene 160°C R,?'- / Scheme ii RsNH 2 i Toluene, reflux, then add TFA (cat) RsNH 2 Dioxane, reflux, then add MSA ( 1 . 0 eq) Scheme 12 o o o R NH 2 Toluene, reflux TFA (cal) Scheme 13 R" 1) NaOH, MeOH/Dioxane 2) HoBt, ( --CDI HNR'R", DMF Polyamine Scheme 14 F-.,.,.S'- F BH 3-Me 2 S o.KiHy THF B r "" 0 °C to rt CI .....,/N <... CI !1 , DMF/CH 2 1) DMF/THF iI 2) HzNNH 2 , Dioxane Scheme DPPA Et 3 N AcCN/t-BuOH (1:1 ) reflux R O 4N HCI Dioxane Scheme 16 (1) ,'/' SnBu 3 Pd(PPh 3) 4 THF, 63 C R O (2) NRIS, CH 2 CI 2 R = halogen Scheme 17 OH Acetone/H 2 0 (3:1) R n=0-6 n=0-6 Scheme 18 OH R1 (1) lead tetraacetate, toluene O /- ._/R (2) NaBH 4 , MeOH R," % ]'I n=0-6 O lead tetraacetate, toluene Jones Reagent, acetone 81% Scheme 19 R X DMF C RNH Scheme R'-... NH OH R'NH 2 i,. neat, 190 C I I R 5 R Scheme 21 NHR'R" Base Base Scheme 22 BnO. H4Pd/MeOH or FPhCH 2 Br ,! L..I 1 /N... HCO 2 NHJPd/MeOH 0 K 2 CO 3/DMF, 110C Br 2 R"PhCH 2 Br Me 2 CO/60C R =BrorCl O Scheme 23 MeOH, H÷ MeO2C Br NBS, benzoyl peroxide, CCI 4 1. BnNH 2 Et 3 N, C 6 H 6 HO2C NBOc 2. H 2, Pd/C 3. BocaO, DMAP 1. Nail. Nal, THF R'BnO. DIBAL m j...j I NBoc Et 2 0, CH 2 CI 2 R'BnO. R O RI=BrorCI RI" " O X= Br or CI 2. H÷ or heat Scheme 24 H CO 1. Et0C0Cl, NMM NCS, AcOH I i, 2. NaBH 4 , H 2 0 H H R 1 = Br or Cl DMF R'Ph,,o. 1. BrCH 2 N'R", Nail, THF R'Ph..o./' D i, OH RI.' NH 2. DMSO, 110 C (if necessay R Nv AdR" to remove Boc group) O R 1 = Br or CI, R 1 = Br or Cl Ar = aryl of heteroaryl Scheme OEt CN \N_ OMe OEt CN conc, H 2 SO 4 MeO /XC / OMe ,. ./ // X C N ' ]J I N --N NC Jl NH MeOH, reflux \ O Rubber Nail. EtSH HO /N .R' NC vR NC" K 2 CO 3 / DMF O O The invention is illustrated further by the following examples, which are not to be construed as limiting the invention in scope or spirit to the specific procedures described in them. Those having skill in the art will recognize that the starting materials may be varied and additional steps employed to produce compounds encompassed by the invention, as demonstrated by the following examples. Those skilled in the art will also recognize that it may be necessary to utilize different solvents or reagents to achieve some of the above transformations. In some cases, protection of reactive functionalities may be necessary to achieve the above transformations. In general, such need for protecting groups, as well as the conditions necessary to attach and remove such groups, will be apparent to those skilled in the art of organic synthesis. When a protecting group is employed, adeprotection step may be required. Suitable protecting groups and methodology for protection and deprotection such as those described in Protecting Groups in Organic Synthesis by Greene and Wuts are well known and appreciated in the art. Unless otherwise specified, all reagents and solvents are of standard commercial grade and are used without further purification. The appropriate atmosphere to run the reaction under, for example, air, nitrogen, hydrogen, argon and the like, will be apparent to those skilled in the art. Examples Example 1 4-(benzyloxy)-i-(4-methylbenzyl)pyridin-2(!H)-one D 4-Benzyloxy-2 (IH) -pyridone (3.0 g, 0. 015 mol) , 4methylbenzyl bromide (3.15 0.17 mol) , and potassium carbonate (3.0 g, 0.022 mol) were heated at 80 °C for 2 hours. Contents were allowed to cool, diluted with water and a solid (5.52 g) was filtered. FABHRMS m/z 306.1494 (M+H, C 20 H 20 NO 2 requires 306.1494). IH NMR (CDCI 3 /300 MHz) : 7.50-7.40 (m, 5H) ; 7.20-7.05 (m, 5H) ; 6.07-6.00 (m, IH) ; 5.95-5.90 (m, IH) ; 5.05 (s, 2H) ; 5.00 (s, 2H); 2.32 (s, 3}{). Anal. Calcd for C 20 HIgNO 2 : C, 78.66; H, 6.27; N, 4.59. Found: C, 78.54; H, 6.38; N, 4.58. Example 2 4 - (benzyloxy) -3 -bromo1 - (4 -methylbenzyl ) pyridin2 (IH) -one The material prepared in Example ! (2.1 g, 0.007 moi) and sodium acetate (738 mg, 0.009 mol) in glacial acetic acld (15 niL) were cooled =o 15 OC .......... om = (0 412 mL, 0 0081 in g_a =_ " - - acetic acid {5 mL) was added dromwise Contents = s irred 2 hours, coming to room temperature. Water (200 haL) was added and a light yellow solid was fil-ered. Mp 150.4 - 15i.2 F/dgHRMS m/z 384.0599 (M+H, C 20 H gBrNO re,aires 384.0601) . H AIMR (CDCI]/300 MHz) 6: 7.42-7.30 (m, 5H) ; 7.22-7.08 (m, 5H) ; 6.02 (d, IH) ; 5.20 (s, 2H) ; 5.12 (s, 2H) ; 2.32 (s, 3H) . Anal. Calcd for C 20 HI BrN0 2 : C, 62.51; H, 4.72; N, 3.65. Found: C, 62 l H a 48. N, 3 54 • ---s ! - • s • • Examples 3-i0 The compounds of Examples 3 - ! 0 are prepared essentially according to the procedure set forth above with respect to Example i. Compounds wherein R = Br are prepared essentially according to the procedure of Example 2. Example M+H m/z FABHRMS No. RI R 2 MF Requires m/z NMR characterization of compounds of Exam.p!es 3-10 IEx. No. I NMR Data i EX. 3 f :H k (CDCl /300 MHz} 6: 7.43 (d, 2H); 7.40-7.33 { H),- 7.207.07 (m, 3H) ; 6.04-6.01 (m, IH): 6.00-5.92 (m, IH) ; 5.03 (s, ! 2H) ; 4.98 (s, 2H) EX. 4 H N-MR {CDC!}/300 MI z) 8: 7.50-7.15 (m, 10H) ; 6.06 id, ill} ; 5.20 (s, 2H) , 5.10 (s, 2H) EX. 5 H NMR (CDC1 3 /300 MHz) 6: 7.40-7.32 (m, 5H); 7.24 (AB quartet, 4H) ; 7.!0 (d, IH); 6.03-6.00 (m, IH) ; 5.98-5.92 (m, IH); 5.03 (s, 2H) ; 4.99 (s, 2H) Ex. 6 H NMR (CDCI /300 z) : 7.43-7.20 (m, 10H} ; 6.08 {d, IH} ; 5.20 I {s, 2H); 5.10 {s, 2H) EX. 7 I H NMR ICDCI /300 M14z) 8: 7.45-7 .25 (m, 5H) ; 7. 12 (d, IH) ; 7.071 6.93 (m, 4H) ; 6.04-6.02 (m, IH) ; 6.00-5.94 (m, IH) ; 5.08 (s, I 2H) ; 5.00 (s, 2H) Ex. 8 IH NMR (CDCI]/300 MHz) 6:7.43°7.25 {m, 6H} ; 7.21 (d, IH) ; 7.106.93 (m, 3H) ; 6.08 (d, IH) ; 5.22 (s, 2H) ; 5.12 (s, 2}{) x. 9 H NMR (CDC /300 Fd{z) 8: 7.43-7.00 (m, 10H) ; 6.01-5.92 (m, 2H) ; 5.10 (s, 2H) ; 4.99 (s, 2H) Ex. i0 ;H NMR (CDC1 3 /300 M z} : 7.52 (d of t, IH) ; 7.44-7.26 (m, 7H) ; 7.15-7.00 {m, 2H) ; 6.03 {d, !H) ; 5.20 {s, 2H} ; 5.15 {s, 2H) Example ii 4- (benzyloxy) -3-bromopyridin-2 (IH) -one H The material of Example ii was prepared according to the procedure of Example 2. IH NMR (CDC1 3 /300 MHz) 8: 7.50-7.30 (m, 6H) ; 6.20 (d, iH); 5.24 (s, 2H). Anal. Calcd for C 2 HI 0 BrNO 2 (0.3H 2 0): C, 50.48; H, 3.74; N, 4.91. Found: C, 50.79; H, 3.41; N, 4.82. Examples 12-19 The compounds of Examples 12-19 are prepared essentially acccrding to the procedures sez fornh above for Examc!e i. Compounds wherein R= = Br are prepared essentially accerdin to the procedure of Example 2. I Examoie M H FABHFsM S I I t i No. R: i R= MF Requires 1 m/z ; EX. i2 -Br {4-. 0854 1 ,benzyloxy 476.0861[ 476 I 13 -H '4-CO 2 Me 350. 1392 350.1391 . 14 -Br 14-CO 2 Me CnHIeBrNO 4 428.0497 428.0480 Ex. 15 !-Br 4-CO 2 H C 20 HI 6 BrN0 4 414.0341 414. 0360 !Ex. 16 -H 4-CN 3 1 7.12901317.1270 C 20 H 6 N O 2 17 -st 4-cN C 20 HIsBrN 2 0 2 395.0395 395.0376 'Ex. 18 -H 4-tButy! C 23 H 2 sNO 2 348.1964 348.1949 'Ex. 19 -Br 4-tButyl C 23 H 24 BrN0 2 426.1069 426.1023 i I. NMR characterization of compounds of Examples 12-19 Ex. No'. NMR Data Ex. 12 *H NMR (CDC1 3 /300 M zi : 7.45-7.15 (m, 13H) ; 6 • 92 (d, 2H) ; 6.01 (d, IH); 5.20 (s, 2H); 5.08 (s, 2}{); 5.03 (s, 2}{) Ex. 13 IH NMR (CDC1 3 /300 M]4z): 8.00 (d, 2H); 7.40-7.25 (m, 7H); 7. (d, 114) ; 6.03-6.01 (m, 114) ; 6.00-5.93 (m, iH); 5.12, (s, 2}{) ; 5.00 (S, 2H) ; 3.95 (s, 3H) Ex. 14 }{ NMR (CDCI /300 MHZ) : 8.00 (d, 2H) ; 7.42-7.31 (rn, 7H) ; 7.23 (d, IH); 6.08 (d, IH); 5.22 (d, 2H); 5.20 (s, 2}{); 3.95 (s, 3}{) • H NMR (DMSO-J 6 /300 M}{z): 8.00-7.80 (mi' 3H) ; 7.53-7.27 (m, 7}{); Ex. 6.50 (d, I}{); 5.32 (s, 2H); 5.20 (s, 2H) Ex. 16 IH NMR (CDC1 3 /300 MHz) 6: 7.60 (d, 2H); 7.42-7.30 (m, 7}{); 7". 13 (d, IH); 6.05-5.98 (m, 2H) ; 5.11 (s, 2H) ; 5.00 (s, 2H) Ex. 17 }{ NMR (CDCI /300 MHz) 5: 7.61 (d, 2H); 7.48-7.30 (m, 6}{); 7.23 (d, 2}{}; 6.12 (d, 1H); 5.22 (s, 2}{); 5.20 (s, 2H) NMR (CDC1 3 /300 MHz) : 7.40-7.28 (m, 7 H} ; 7.20 (d, 2H) ; 7.10 Ex. 18 (d, 1}{) ; 6.02 (d, 1H) ; 5.97-5.90 (m, IH) ; 5.02 (d, 2H) ; 4.98 (d, 2H) Ex. 19 i}{ NMR (CDC1 3 /300 M z) 5: 7.43-7.20 (m, I0}{) ; 6.02 (d, IH) ; 5.20 (s, 2H) ; 5.10 (s, 2H) ; 1.30 (s, 9H) Example 4-(benzyloxy)-3-bromo-l-ethy!pyridin-2(IH)-one l<N'% 0 To 4-benzyloxy-2(!H)-pyridone (I.0 g, 0.005 moi) and potassium carbonate (i.0 g, 0.007 mol) in DMF (!0 mL) was added bromoethane (0.82 mL, 0.0!! mol). Contents were heated at 75°C overnight. Contents were allowed to coo! and partitioned between EtOAc and water. The E=OAc layer was dried over MgSO 4 , filtered, and concentrated in vacuo leaving a waxy solid, which was recrystallized from EtOAc/hexanes to give a white solid (720 mg). To the white solid (700 mg, 0.003 mol) in glacial acetic acid (i0 mL), bromine (0.17 mL, 0.00325 mol) in glacial acetic acid (5 mL) was added dropwise at 15°C. Contents were stirred one hour at room temperature and a yellow solid (I.I g) was filtered. The solid was partitioned between EtOAc and 2.5N sodium hydroxide. The EtOAc layer was dried over MgSO 4 , filtered, and concentrated in vacuo leaving a colorless oil (710 mg), which solidified. FABHRMS m/z 310.0267 (M+H, C 14 H 1 sBrNO 2 requires 310.0263) . IH b'MR (CDCI /300 MHz) 6: 7.45-7.30 (m, 6H) ; 7.22 (d, IH) ; 6.07 (d, 1H); 5.20 (s, 2H) ; 4.00 (q, 2H); 1.32 (t, 3H). Anal. Calcd for C 14 H 4 BrN0 2 : C, 54.56; H, 4.58; N, 4.55. Found: C, 54.21; H, 4.38; N, 4.43. Example 21 3 -bromo4 - hydroxy1 - (4 -hydroxybenzyl ) pyridin2 (IH) -one The material of ExamPle 12 (120 mg, 0.25 mmo_) and 10% pa!ladium/carbon (30 mg) in glacial acetic acid (2 mL) were shaken at 55 ibs of hydrogen for 4 hours. Con-ents were filtered and the filtrate was concent -aEed in vacua ieavzng an oil. FABHRMS m/z 295.9952 (M÷H, C= 2 Ht BrNO 3 reauires 295.9922) . :H NM R (DMSO-d 6 /300 MHz) 6: 11.40 (br s, ill) ; 9.40 {hr s, IH) ; 7.60 (d, !H) ; 7.10 (d, 2H) ; 6.70 (d, 2H) ; 6.02 (d, IH ; 4.93 (s, 2H) . Anal. Calcd for C! 2 H,_ 0 BrNO 3 (1.4 H 2 0) : C, 44.85; H 4.02; N, 4.36. Found: C, 45.07; H, 4.10; N, 4.35. Example 22 4-(benzyloxy)-B-bromo-l-methylpyridin-2(iH)-one hydrobromide H-St N O To 4-benzyloxy-2(lH)-pyridone (1.0 g, 0.005 mol) and otassium carbonate (760 mg, 0.0055 mo!) in DMF (10 mL) was added methyl iodide (0.342 rr&, 0.0055 mol). Contents were stirred overnight. Contents were partitioned between EtOAc and water. The EtOAc layer was dried over MgS0 4 , filtered, and concentrated in vacuo leaving a white solid (960 mg). To the white solid (332 mg, 0.0015 mol) in glacial acetic acid (I0 mL), bromine (256 mg, 0.0016 mol) in glacial acetic acid (5 mL) was added dropwise at 15°C. Contents were stirred one hour at room temperature and the desired was filtered as a white solid, 262 mg (59% yield), mp I05.3-I05.6°C. FABHRMS m/z 296.0097 (M+H, C 13 HI 3 BrNO 2 requires 296.0110). IH NMR Anal. Calcd for C: 3 HI BrNO (HBr, 0.3H O): C, 41.04; H, 3.60; N, 3.68. Found: C, 41.00; H, 3.87; N, 3.52. Example 23 4- (benzyloxy) -3-bromo1-methylpyridin-2 (1H) -one The material of Example 22 was partitioned between EtOAc and 2.5N sodium hydroxide. The EtOAc layer was dried over MgSO 4, filtered, and concentrated in vacuo leaving a red oil, which solidified. FABh'RMS m/z 294.0!12 (M+H, Cz 3 HnBrNO 2 requires 294.0130) . ZH NMR (CDC1 3 /300 MHz) : 7.45-7.30 (m, 6H) ; 7.22 (d, IH) ; 6.07 (d, IH) ; 5.20 (s, 2H) ; 4.00 (q, 2}{) ; 1.32 (t, 3H). Anal. Calcd for Cz 3 H 2 BrNO 2 : C, 53.08 ; H, 4. i! ; N, 4.76. Found: C, 53.06; H, 4.20; N, 4.74. Example 24 4-{ [4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)-yl]methyl}- N'-hydroxybenzenecarboximidamide NOH NH 2 The material of Example 17 (500 mg, 0.00127 mol), hydroxylamine hydrochloride (90 mg, 0.0013 mol) and sodium bicarbonate (109 mg) were refluxed in ethanol (15 mL) overnight. Contents were allowed to cool and a solid was filtered and washed with water to give the desired as a white solid, 447 rag, (82% yield), mp 210.2-212.2 °C FABHRMS m/z 428. 0634 (M+H, C 20 HzgBrN 3 0 3 requires 428. 0610) . IH NMR (DMSO-d 6 Example 4 - {benzyloxy} - 3-bromo-!- (piperidin-4-ylmethyl) pyridin2(iH)-one hvdrochioride " NH H-CI To the material of Example ii (924 mg, 0.0033 mo!) in DMF (5 mL) was added dropwise sodium bis(trimethylsily!)amide (IM in THF, 3.6 mL). Contents were stirred one hour before adding dropwise a solution of 4 -methane sul fonyloxymethyl - 1 - piperidine-l-carboxylic acid tert-butyl ester (J. Labelled Compd, Radiopharm, 38 (7) , 1996, 595-606) (I.0 g, 0.0036 tool) in DMF (5 mL) . Contents were heated at 75°C overnight. Contents were allowed to cool and poured into water (I00 mL). A solid was filtered and recrystallized from EtOAc to give white crystals (546 mg). The white crystals were refluxed in 4 N HCl/dioxane (i0 mL) for 3 hours, allowed to cool and filtered to give the desired as a white solid, 415 mg (30% yield), mp 207.9°C. FABHRMS m/z 377.0852 (M+H, CIeH 23 BrCIN O 2 requires 377.0865) . H NMR (DMSO-d 6 /300 MHz) 6: 8.90 (br, IH) ; 8.64 (br, IH) ; 7.80 (d, IH) ; 7.50-7.30 (m, 5H) ; 6.48 (d, IH) ; 5.30 (s, 2H) ; 3.83 (d, 2H) ; 3.20 (d, 2H) ; 2.88-2.64 (m, 2H) ; 2.10-1.90 (m, IH) ; 1.60 (d, 2H) ; 1.50-1.40 (m, 2H). Anal. Calcd for C 18 H 22 BrCIN 2 0 2 (0.3 H 2 0) : C 51.58; H, 5.43; N, Example 26 4- (benzyloxy) -I- [4- (trif!uoromethyl)benzy!] pyridin-2 one {r A L.N 0 The material of Example 26 was prepared according procedure of Example !. FABHRMS m/z 360.1213 (M÷H, C requires 360.1211). IH NMR (CDCI /300 MHz) 6: 7.60 (d, 7.41-7.30 (m, 7H) ; 7.13 (d, IH) ; 6.05-6.01 (m, IH) ; 6.00-5.95 (m, IH); 5.13 (s, 2H) ; 5.00 (s, 2H). Anal. Calcd for C 20 HI FaNO 2 : C, 66.85; H, 4.49; N, Found: C, 66.64; H, 4.26; N, 3.93. Example 27 4- (benzyloxy) -3-bromo-l- [4- (trifluoromethyl) benzyl ] pyridin-2 (IH) -one The material of Example 27 was prepared according procedure of Example 2. FABHRMS m/z 438. 0308 C 20 HI BrFHNO= requires 438.0316) . iH NMR (CDC1 3 /300 MHz) 7.65-7.20 (m, 10H) ; 6.13-6.03 (m, IH) ; 5.30-5.13 (m, 4H). Anal. Calcd for C 20 H:sBrF 3 NO=: C, 54.81; H, 3.45; N, Found: C, 54.69; H, 3.34; N, 3.19. Example 28 2(!H)-one hydroch!oride -. N - L 0 H-CI \N j; H To the material of Example ll (3.1 g, 0.011 moi) in DMF (20 mL) was added dropwise sodium bis(trimethylsi!yl)amide (iM in THF, 12 mL) . Contents were stirred one hour before adding dropwise a solution of 3-methanesulfony!ox -methyl-lpiperidinel-carboxylic acid ert-butyl ester (Bioorg. Med. Chem. Le t, 8(13) , 1998, 1595-1600) (4.2 g, 0.015 tool) in DMF (5 mL). Contents were heated at 75°C overnight. ContenTs were allowed to cool, poured into water (i00 mL) and a solid was f peered. The solid was st Erred in 4 N HCl/dioxane (!5 mL) for 3 hours and filtered to give the desired as a white solid, 752 mg (18% yield) . mp 138.1- 139.2°C. FABHRMS m/z 377. 0859 (M+H, C 1 sH=:BrN:O 2 requires 377.0865) . iH NMR (DMSO-d 6 /300 MHz) : 9.50-9.10 (br, 2H) ; 8.00 (d, IH) ; 7.50-7.30 (m, 5H] ; 6.93 (d, IH) ; 5.30 (s, 2H) ; 4.30-3.90 (m, 3H) ; 3.40-3.10 (m, 3H) ; 2.80-2.50 (m, 3H) ; 2.402.00 (m, IH) ; 1.90-1.60 (m, 4H) ; 1.40-1.10 (m, IH) . Anal. Calcd for CIBH BrN 2 0 2 (2HCI, 0.25 H 2 0) : C, 47.55 ; H, 5.21; N, 6.16. Found: C, 47.48; H, 5.46; N, 6.27. Example 29 4-(benzyloxy)-3-bromo-l-(2-thien-3-ylethyl)pyridin-2(IH)- To the material of Example !! (500 mg, 0.0018 mol) in DN? (5 mL) was added dropwise sodium bis(trimethy!sily!)amide (IM in THF, 2 mL) . Contents were stirred one hour before adding dropwise a solution of methanesulfonic acid 2-thiophen-3-ylethyl ester (J.A.C.S, !09(6), 1987, 1858-1859) (412 mg, 0.002 mo!) in DMF (5 mL). Contents were heated at 75°C overnight. Contents were allowed to cool, poured into water (i00 mL), and extracted into EtOAc, dried over MgS0 4 , filtered, and concentrated in vacuo leaving a light yellow oil. The oil was purified by silica gel chromatography eluting with 50% EtOAc/hexanes to give the desired as a white solid, 199 mg (28% yield), mp 134.0-!34.3°C. FABHRMS m/z 390. 0144 (M+H, CIsHI BrNO 2 S requires 390.0163) . H NMR (CDC1 3 /300 MHz) : 7.43-7.20 (m, 6H) ; 6.92-6.80 (m, 3H) ; 5.90 (d, IH) ; 5.20 (s, 2H) ; 4.13 ( 2H) ; 3.10 (t, 2H). Anal. Calcd for C 18 HI BrNO 2 S: C, 55.39; H, 4.13; N, 3.59. Found: C, 55.21; H, 3.87; N, 3.52. Example 4 - (benzyloxy) - 3 - bromo1 - (2 -thien-2 -ylethyl ) pyridin2 (IH) -one The title compound was prepared essentially according to the procedure of Example 29. mp 128.0-129.5°C. FABHRMS m/z 390. 0160 (M+H , C:aH: =.NO S requires . 290 • 0163) • :'" -'- -k.rM R (CDC1 3/300 MHz) 6: 7.48-7.30 (m, 5H); 7.12 (d, !H); 6.95-6.80 (m, 2H); 6.75-6.68 (m !H); 5.95 (d, !H); 5.20 (s, 2H); 4.16 (t, 2H); 3.30 (t, 2H) . nal. Calcd for C 18 HI BrNO 2 S : C, 55.39; H, 4.13; N, 3 . 59. Found: C, 55.06; H, 4.0-; N, 3.56. Example 31 4Cbenzyloxy) -3-bromoI- [3- (tr fluoromethyl) benzyl] pyridin2 (IH) -one F 3 C To the material of Example !I (500 mg, 0.0018 mol) in DMF (5 mL) was added dropwise sodium bis(trimethylsilyl)amide (IM in THF, 2 mL) . Contents were stirred one hour before adding dropwise a solution of 3-trif!uoromethylbenzyl bromide (478 mg, 0.002 mol) in DMF (5 mL). Contents were heated at 75°C for 2 hours. Contents were allowed to cool, poured into water (i00 mL), and extracted with EtOAc, which was dried over MgSO 4 , filtered, and concentrated in vacuo leaving a white solid. FABHRMS m/z 438.0301 (M+H, C 20 HI 6 BrF 3 NO 2 requires 438.0316). IH NMR (CDCI /300 MHz) : 7.60-7.20 (m, 10H) ; 6.10 (d, IH) ; 5.14 (s, 2H) ; 5.20 (s, 2H). Anal. Calcd for C 20 HIsBrF 3 N0 2 : C, 54.81; H, 3.45; N, 3.20. Found: C, 54.81; H, 3.36; N, 3.13. Example 32 4 - (benzyloxy) -3 -bromo1 - [2 - (tri fluoromethyl ) benzyl] pyridin-2 (IH) -one The material of Example 32 was prepared accordinc to procedure of Example 31. FABHRMS m/z 438.0280 (M+H, C 20 H= BrF 3 NO 2 re ires 438.03!6) NMR (CDC1 3 /300 FuHz) 5: 7.68 (d, IH) ; 7.55-7.20 (m, 8H) (d, !H) ; 6.10 (d, !H) ; £.40 (s, 2H) ; 5.13 (s, 2H) . Anal. Calcd for C 20 H:sBrF;N© 2 : C, 54.81; H, 3.45; N, Found: C, 54.48; H, 3.36; N, 3.17. Example 33 4- (benzyloxy] ~ I- [4- (trifluoromechoxy) benzyl] pyridin2 (IH) -one i The materia! of Example 33 was prepared according procedure of Example I. FABHRMS m/z 376.1158 (M+H, C 20 HI F 3 NO 3 requires 376.1161) NMR (CDC1 3 /300 MHz) 6: 7.40-7.05 (m, 10H) ; 6.05-5.95 (m, 5.06 (s, 2H) ; 4.98 (s, 2H). Anal. Calcd for C 20 H FHNO 3 : C, 64.00; H, 4.30; N, Found: C, 63.97; H, 4.26; N, 3.57. Example 34 4-(benzyloxy)~3-bromo-l-[4-(trifluoromethoxy) benzyl]pyridin-2(iH)-one The material of Example 34 was prepared according to =he procedure of Example 2. FABHRMS m/z 454.0240 (M+H, C 20 H: 6 BrF N0 3 requires 454.0266). b-MR (CDC1 3 /300 MHz) 6: 7.45-7.10 (m, 10H) ; 6.08 (d, IH) ; 5.20 (s, 2H) ; 5.12 (s, 2H) . Anal. Ca!cd for C 20 HIsBrF 3 N0 3 : C, 52.88; H, 3.33; N, 3.08. Found: C, 52.53; H, 3.09; N, 2.92. Example l-benzyl-4-(benzyloxy)-6-methylpyridin-2(!H)-one CH: O" HI Step 1 : Preparation of 1 - benzyl4 - hydroxy- methylpy-ridin-2 (IH) -one. 4 -hydroxy6 -methyl - 2-pyrone (0.2 mol, 25.2 g) and benzylamine (0.2 mol, 21.4 g) were added to water (800 mL) and heated to reflux with stirring for 2 hours. After cooling room temperature, a light brown solid was collected filtration. (33.4 g, 77%): IH NMR (DMSO-d /300 MHz) 6: 10.5 requires 216.102). Step 2: Preparation of i-benzy!-4- (ben=y!oxv)-6- mezhylpyridin2 (IH) -one. l-benzy!-4-hydroxy-6-methy!pyridin-2 (!H)-one (i0 mmo!, 2.!5 g) , dichloromethane (!00 mL) , benzy!bromide (!I mmo!, !. 88 g) , sodium hydroxide (2.5 N, 20 mmol, 8 mL) , and benzylt riethylammonium chloride (0.5 g) were vigorously stirred at room temperature for !6n. Hydrochloric acid (i N) was added until the mixture produced an acidic reaction to pH paper. The mixture was then extracted with ethyl acetate (3 X mL) . The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated. The product was obtained by flash chromatography eluting with ethyl acetate : hexanes (1:2) . The appropriate fractions were concentrated to a clear oil. (!.3 g, 43%) : IH N-MR (DMSOd 6/300 M/£z) 6: 7.4-7.1 (m, i0 H), 6.0-5.9 (m, 2H) , 5.2 (s,2H), 5.1 (s, 2H) , 2.2 (s, 3H) . ESHRMS m/z 306. 147 (M+H, C 20 HIgNO 2 requires 306.149) . Example 36 l-benzyl-4-(benzyloxy)-3-bromo-6-methylpyridin-2(1H)-one The product from example 35, !-benzy!-4-(benzyloxy)-6methyipyridin-2(!H)-one (4.2 mmol, 1.3 g), acetic acid (50 mL), and sodium acetate (5.0 mr.o!, 0.41 g) were stirred a room temperature. Bromine (4.2 mmo!, 0.67 g) was added drop wise wish stirring. After hour, water (I00 mL) was added and the mixture was extracted with ethyl acetate (3 X 50 mL) . The combined organic extracts were washed with saturated aqueous sodium bicarbonate sc!ution and brine. After drying over magnesium sulfate and concentrating, the mixture was purified by flash column chromatography eluting with ethyl acetate : hexanes (I : 2). The appropriate fractions were concentrated to yield a light oil. (i.0 g, 62%): IH N-MR (DMSO-d /300 M z) 7.4-7.0 (m, i0 H), 6.5 (s, ill), 5.29 (s,2H) , 5.27 (s, 2H) , 2.2 (s, 3H) . ESHRMS m/z 384.057 (M+H, C 20 HIsNO 2 Br redirect 384.060) . Example 37 l-benzyl-4-(benzyloxy)-3,5-dibromo-6-methylpyridin-2(iH)- one O" r The product from example 35, l-benzy1-4-(benzyloxy)-6methylpyridin-2(IH)-one (4.2 mmol, 1.3 g), acetic acid (50 ), and sodium acetate (5.0 mmol, 0.41 g) were stirred at room temperature. Bromine (4.2 oi, 0.67 g) was added drop wise with stirring. After M hour, water (I00 2) was added and the mixture was extracted with ethyl acetate (3 X 50 ). The combined organics were washed with saturated aqueous sodium bicarbonate solution and brine. After drying over magnesium sulfate and concentrating, the mixture was purzfzed by flash column chromatography eluting with ethy! acetate : hexanes (i : 2). The appropriate fractions were concentrated to yield a white solid. (0.3 g, 15%): H N MR (DMSO-d 6 /300 MHz) 7.5-7.0 (m, !0 H) , 5.42 (s,2H) , 5.07 (s, 2H), 2.45 (s, 3H). ESHRMS m/z 463.966 (M+H, C 20 HI NO 2 Br 2 requires 463.968). Example 38 l-benzy!-4-[(3-chlorobenzyl)oxy]-6-methylpyridin-2(1H)- one H 3 C 0 Step i: Preparation of 1-benzyl-6-methyl-2-oxo-l,2dihydropyridin-4-yl 4-bromobenzenesulfonate. l-benzyl-4-hydroxy-6-methylpyridin-2(iH)-one (from example 35) (I0 mmol, 2.15 g), N,N'-dimethylformamide (30 mL), potassium carbonate (20 mmo!, 2.76 g), and 4bromobenzenesulfonyl chloride (I0 mmol, 2.55 g) were stirred at room temperature for 16 hours. Hydrochloric acid (IN) was added until the mixture was acidic to pH paper. Brine (50 mL) was added and the mixture extracted with ethyl acetate (3 X mL) . The combined organic extracts were washed with brine and dried over magnesium sulfate, and filtered. After concentrating, the material was purified by flash column chromatography eluting with ethyl acetate:hexanes (1:2). The appropriate fractions were concentrated to a clear oil, which solidified upon standing several days to a white solid. (3.3 g, 76%) : iH NMR (DMSO-d /400 MHz) 7.9 (m, 4H), 7.32-7.00 (m, 5H), 7.3 (m, IH) , 6.12 (d, J = 2.4 Hz, ill), 6.02 (J, J = 2.8 Hz, !H), 5.20 (s, 2H), 2.2 (s, 3H) . ESHRM..S m/z 436.002 (M H, C! 9 HI 6 NO SBr requires 436.004) . Step 2: Preparation of l-benzyl-4- [(3-chlorobenzyl)oxy]- 6-methylpyridin-2(iH)-one. -benzyl-6-methyl-2-oxo-l,2-dihydropyridin-4-yi 4bromobenzenesulfonate (3.0 mmol, 1.3 g), N,N'- dimethylformamide (30 mL), 3-chlorobenzyl alcohol (3.0 mmol, 0.43 g) , and sodium hydroxide (60%, 3.3 mmol, 0.13 g) were stirred at room temperature under nitrogen for 4 hours. Hydrochloric acid (I N, I0 mL) was added and the mixture extracted with ethyl acetate (3 X 25 mL) . The combined organic extracts were washed with saturated aqueous sodium bicarbonate solution and brine. After drying over magnesium sulfate and concentrating, the mixture was purified by flash column chromatography eluting with ethyl acetate:hexanes (I:i) to obtain a light yellow oil. (14.3 g, 64%}: IH NMR (DMSOdJ300 MHz) 6:7.4-7.0 (m, i0 H), 6.0-5.8 (m, 2H), 5.2 (s,2H), 5.0 (s, 2H), 2.1 (s, 3H). ESHRMS m/z 340.110 (M+H, C 20 HI 0 NO 2 CI requires 340.110). Example 39 l-benzyl-3-bromo-4-[(3-chlorobenzyl)oxy]-6-methylpyridinThe product of example 38 (SC-%3316), l-benzyl-4- [ (3chlorobenzy! oxy]-6-methylpyridin-2(!H)-one (0.91 mmol, 310 Mg), acetic acid (20 mL), and sodium acetate (0.91 mmol, Mg) were stirred at room temperature when bromine (0.91 mmol, 145 Mg) was added. After stirring for one hour, the mixture was concentrated, dissolved in ethyl acetate, and washed successively with saturated aqueous sodium bicarbonate solution, brine, and water. After drying over magnesium sulfate and concentrating, the product was recrystallized from tetrahydrofuran / hexanes to yield a white solid. (240 Mg, 63%): IH NMR (DMSO-d 6 /300 MHz) 7.6-7.0 (m, I0 H), 6.5 (s, ill) , 5.33 (s,2H) , 5.33 (s, 2H) , 2.3 (s, 3H) . ESHRMS m/z 420.019 (M+H, C 20 HIvNO 2 BrCI requires 420.019) . EXAMPLE 1 -Benzyl-4 - [2,6 - (dichlorobenzyl) oxy] pyridin2 (IH) -one The title compound was prepared essentially as described in claim i. mp 151.6-152.0 °C. IH NMR (CDCI 3 /300MHz) 6: 7.31 (m, 8H), 7.12 (d, IH, J = 7.45 Hz), 6.13 (d, IH, J = 2.42 Hz), 5.90 (dd, IH, J = 2.62 Hz), 5.22 (s, 2H), 5.10 (s, 2H) . ESHRMS m/z 360.0551 (M+H CIgHIsCI 2 N0 2 requires 360.0558). EXAMPLE 41 1 -Benzyl - 3 -bromo4 - [2,6 - (dichlorobenzyl) oxy] pyridin2 (IH) -one l-Benzyl-4-[2,6-(dichlorobenzyl)oxy]pyridin-2(iH)-one (0.400 g, I.II mmol) was dissolved in acetic acid (I0 mL) . Sodium acetate (0.091 g, I.Ii mmol was added, and the mixture was cooled to 15 °C. Bromine (0.195 g, 1.22 mmol) was added via syringe. The reaction stirred at room temperature for 2 hours. Water (15 mL) was added, and the mixture transferred to a separatory funnel. Ethyl acetate (50 mL) was added and the layers were separated. The organic phase was washed with aqueous NaHCO 3 (2 x 25 mL), dried over MgSO 4 , filtered, and evaporated to yield a white solid. IHNMR (CDCI 3 /300MHz) 6: 7.34 (m, 9H), 6.24 (d, IH, J = 7.65 Hz), 5.37 (s, 2H) , 5.18 (s, 2H) . ESHRMS m/z 439.9646 (M+H C 19 HI 4 BrCI 2 N0 2 requires 439.9641). Example 42 i-BenzyL-4-[(2-chlorobenzyl)oxy]pyridin-2(iH)-one The title compound was prepared by a procedure similar to the one described in Example i. mp 124.6-125.0 °C. IHNMR (CDCI 3/300MHz) 6:7.36 (m, 9H), 7.14 (d, IH, J = 7.65 Hz , 6.04 (d, IH, J = 2.62 Hz) , 5.98 (d, IH, J = 2.82 Hz), 5.10 (s, 2H) , 5.09 (s, 2H) . ESHRMS m/z 326.0950 (M+H C 19 HI 6 CINO= requires 326.0948). Anal. Calc'd. for CIgHIGCINOa: C, 70.05; H, 4.95; N, 4.30; CI, 10.88. Found: C, 69.87; H, 4.74; N, 4.42, CI, 11.08. EXAMPLE 43 l-Benzyi-3-bromo-4- [ (2-chlorobenzyl) oxy] pyridin-2 (IH) -one The title compound was prepared by a procedure similar to the one described in Example 2. mp 143.3-145.5 °C. IHNMR• (CDCI /300MHz) 6:7.63 (d, 2H, J = 1.81 Hz), 7.44 (m, 9H), 6.06 (d, IH, J = 7.65 Hz), 5.29 (s, 2H), 5.17 (s, 2H) . ESHRMS m/z 406.0036 (M+H C 19 HIsBrCINOa requires 406_.0032). EXAMPLE 44 l-Benzyi-3-bromo-4- [ (4-methylbenzyl)oxy] pyridin-2 (IH) -one The title compound was prepared by a procedure similar the one described in Example 2. mp 149.0-149.7 °C. IHNMR (CDCI /300MHz) 6: 7.25 (m, 10H), 6.04 (d, IH, J = 7.65 Hz) 5.17 (s, 2H), 5.15 (s, 2H), 2.34 (s, 3H). ESHRMS m/z 386.0583 (M+H C 20 HIsBrNO requires 386.0581). EXAMPLE l-Benzyl-4- [ (3-chlorobenzyl) oxy] pyridin-2 (IH) -one The title compound was prepared by a procedure similar the one described in Example i. mp 95.5-95.7 °C. IHNMR 2H) .. ESHRMS m/z 326.0977 (M+H C 19 HI 6 CINO 2 requires 326.0948) . EXAMPLE 46 1 -Benzy1-4 ~ -3 -bromopyridin-2 (IH) -one The title compound was prepared by a procedure similar to the one described in Example 2. mp 180.6-182.1 °C. IHNMR (CDCI]/300MHz) 6: 7.33 (m, 10H), 7.14 (d, IH, J = 7.45 Hz), 6.08 (d, IH, J = 7.45 Hz), 5.13 (s, 2H) , 4.15 (s, 2H) . ESHRMS m/z 386.0211 (M+H C 19 HI BrNOS requires 386.0214). EXAMPLE 47 l-Benzy1-3-bromo-4- { [2- (trifluoromethyl) benzyl] oxy}pyridin-2 (IH) -one The title compound was prepared by a procedure similar to the one described in Example 2. mp 133.2-133.5 °C. IHNMR IH, J = 7.85 Hz) , 5.39 (s, 2H) , 5.16 (s, 2H) . ESHRMS m/z 438.0313 (M+H C 20 HIsBrF 3 NO 2 requires 403.0316). Example 48 1-benzyl-4-(benzyloxy)-3-iodopyridin-2 iH)-one I, O A mixture of N,O-dibenzyl-2-pyridone 2.0 g, 6.87 mmol), N-iodosuccinimide (1.7 g) , dichloroacetic acid (0.15 mL) in acetonitrile (40.0 mL) was heated at 65 °C under argon atmosphere for 3.5 h, with constant stirring. The reaction mixture was concentrated to dryness, and the residue was purified by silica gel flash chromatography using EtOAc/ hexanes I:I v/v to give the title compound 2.3 g (80%) as a flaky white solid: IH-NMR (CDCI 3 ) 6: 7.4 - 7.2 (m, i0 H), 7.19 (iN, d, J = 7.6 Hz), 5.95 (d, IH, J = 7.6 Hz), 5.2 (s, IH) , 5.15 (s, 2H); ER-MS m/z = 418 (MH ÷); HR-MS m/z calcd C 19 HITNO 2 418.0304, found 418.0277. Example 49 l-benzyl-4-(benzyloxy)-3-vinylpyridin-2(iH)-one A solution of l-benzyl-4-(benzyloxy)-3-iodopyridin-2(iH)- one (1.9 g, 4.56 mmol) and vinyl-tri-butyltin (2.5 mL) in acetonitrile (20 0 mL) containing DMF (2.0 mL) was degassed using house vacuum and purged with argon. Then added PdCI 2(PPh 3) 2 (0.3 g) and the mixture was heated at 65 °C under argon atmosphere for 4 h, with stirring. The solvents were distilled in vacuo, and the residue was triturated with EtOAc and filtered through a pad of celite. The filtrate was concentrated and the residue was purified by silica gel flash chromatography using 25% EtOAc in hexanes to give the title compound (0.75 g. 50%) as an orange colored solid. IH-NMR (CDCI 3 ) 6: 7.4 - 7.2 (m, I0 H), 7.14 (d, IH, J = 7.6 Hz), 7.05 (dd, IH, J = 12.0 Hz) , 6.47 (dd, IH, J = 2.8 Hz), 6.07 (d, IH, J = 7.6 Hz), 5.4 (dd, IH, J = 2.8 Hz), 5.13 (s, 4H) ; ER-MS m/z = 418 (MH ÷) ; ER-MS m/z = 318 (MH +) ; HR-MS m/z calcd C 21 HH 0 NO 2 318.1494, found 318.1480. Example l-benzyl-4-(benzyloxy)-3-ethylpyridin-2(IH)-one To a solution of l-benzyl-4-(benzyloxy)-3-vinylpyridin2 (1H)-one (0.5 g, 1.6 mmol) in EtOH (I0.0 mL) and EtOAc (I0.0 mL) was added Pd/C (I0 %, 0.25 g) and stirred in an atmosphere of hydrogen gas at 30 psi for 16 h. The catalyst was removed by filtration, the filtrate was concentrated to dryness and the resulting residue was purified by silica gel flash chromatography using EtOAc/hexanes (i:i, v/v) to afford the title compound (0.32 g, 64%) as a pale yellow powder: IH-NMR (CD 3 OD) 8:7.52 (d, IH, J = 7.6 Hz), 7.397.2 (m, i0 H), 6.41 (d, lh, J = 7.6 Hz), 5.18 (s, 2H), 5.15 (s, 2H), 2.58 (q, 2H, J = 7.2 Hz), 1.03 (t, 3H, J = 7.2 Hz), ER-MS m/z = 320 (MH +) ; HR-MS m/z calcd C 21 H 22 N0 2 320.1651, found 320.1648. Example 51 3 - acetyl - 4 - (benzyloxy) - 1 - ( 2 - chlorophenyl ) - 6 - methylpyridin-2(iH)-one o% Me Step A Preparation of 3-acetyl-l-(2-chlorophenyl)-4-hydroxy-6methylpyridin-2(iH)-one 0 OH CI A mixture of 2-chlorophenylisocyanate (3.0 g, 19.53 mmol), and diketene (3.3 g, 39.28 mmol) in toluene (i0.0 mL) containing triethylamine (0.05 mL) was heated to reflux for 6 h, under an atmosphere of argon. Toluene was distilled in vacuo and the resulting residue was purified by silica gel flash chromatography using 25 % EtOAc in hexanes as the eluent to afford the title compound (0.85 g, see ref: Heterocycles 27 Step B Preparation of 3-acetyl-4-(benzyloxy)-l-(2-chlorophenyl)- 6-methylpyridin-2(iH)-one To a solution of 3-acetyl-l-(2-chlorophenyl)-4-hydroxy-6methylpyridin-2(iH)-one ( 0.56 g, 2.02 mmol) in DMF (5.0 mL), benzyl bromide (0.3 mL) and potassium carbonate (0.3 g, 2.16 mmol) were added. The mixture was stirred at room temperature for 3 h, and at 65 °C for 1 h under argon atmosphere. The reaction mixture was concentrated in vacuo and the residue was partitioned between 5% citric acid (25 mL) and EtOAc (50.0 mL) . The organic phase was washed with brine, dried (Na 2 SO 4 ), filtered, and concentrated to dryness. The resulting residue was purified by silica gel flash chromatography using 50% EtOAc in hexanes to afford the title compound (0.58 g, 75%) as a pale yellow amorphous substance: IH-NMR (CD 3 OD) 6: 7.65 - 7.3 (m, 9H), 6.5 (s, IH) , 5.31 (s, 2H), 2.42 (s, 3H), and 2.01 (s, 3H) ; ER-MS m/z = 368 (MH ÷); HR-MS m/z calcd C 21 HIgNO CI ,368.1060, found 368.1053. Example 52 l-benzyl-3-bromo-4-(2-phenylethyl)pyridin-2(iH)-one Br Step A Preparation of l-benzyi-3-bromo-4-hydroxypyridin-2(IH)- one A suspension of N-benzyl-4-hydroxy-2-pyridone ((0.75 g, 3.7 mmol), NBS (0.7 g, 1.05 mmol) in dichloromethane was stirred at room temperature for 1.5 h under argon atmosphere. It was diluted with dichloromethane (25 mL), cooled and filtered. The solids were washed with dichloromethane and dried in vacuo. The filtrate and the washings were combined and washed with water, dried (Na 2 SO 4 ), filtered, and concentrated to dryness. The resulting residue was washed with EtOAc, and dried in vacuo to give a combined mass of 0.65 g of the title compound as a white powder: IH NMR (CD OD) 6: 7.54 (d, IH, J = 7.6 Hz), 7.27 (m, 5H), 6.12 (d, IH, J = 7.6 Hz), 5.15 (s, 2H) ; ES-MS: m/z = 280 (MH÷) . Step B Preparation of l-benzyI-3-bromo-2-oxo-l,2-dihydropyridin4-yl t ri f luoromethanesul fonat e To a cold (-30 °C ) suspension of 1-benzyl-3-bromo-4hydroxypyridin-2(iH)-one (0.78 g, 2.8 mmol) in dichloromethane (i0.0 mL), was added triethylamine (0.6 mL, 4.28 mmol ), followed by the addition of triflic anhydride (0.7 mL, 4.17 mmol). The resulting mixture was stirred at -30 °C under argon atmosphere for 1 h. The reaction mixture was then poured into ice/water mixture (50 mL) and the products were extracted with dichloromethane (2 x 25 mL). The combined organic extracts were washed with water (2 x 20 mL), dried (Na 2 S0 4), filtered, and concentrated to dryness. The residue was dried in vacuo to afford the desired trifluorosulfonate (i.0 g) as a pale yellow solid which used as such in the next step: IHNMR (CDCI 3 ) 6: 7.35 (m, 6H), 6.26 (d, IH, J = 8.0 Hz) ; 19FNMR (CDCI ) 6: -73.73 ppm; ES-MS: m/z = 412 (MH÷). Step C Preparation of l-benzyl-3-bromo-4-(phenylethynyl)pyridin2 (iH)-one. Br. To a solution of l-benzyl-3-bromo-2-oxo-l,2dihydropyridin-4-yl trifluoromethanesulfonate (I.0 g) in DMF (5.0 mL) was added phenylacetylene (0.4 mL) and degassed using house vacuum. The reaction flask was then purged with argon, added diis0Propylethylamine (0.53 mL), and PdCl 2 (PPh 3 ) 2 (0.35 g) were added. The resulting mixture was stirred at room temperature for 15 min and heated at 65 °C under an argon atmosphere for 3h. The dark colored reaction mixture was concentrated in vacuo, and the residue was partitioned between EtOAc (50 mL) and 5% aqueous citric acid (25 mL). The organic extracts were washed with water, dried (Na 2 S0 4 ), filtered, and concentrated to dryness. The resulting material was purified by silica gel flash chromatography using 25% EtOAc in hexanes as the eluent The appropriate fractions were combined, concentrated under reduced pressure. IH NMR (CDCI 3 ) 6: 7.57 (m, 2H), 7.38 (m, 8H), 7.21 (d, IH, J = 6.8 Hz), 6.25 (d, IH, J = 6.8 Hz) , and 5.16 (d, 2H) , ES-MS: m/z = 364 (MH÷) ; HR-MS m/z (MH÷) calcd C 20 HIsNOBr 364.0337, found 364.0337. Step D Preparation of l-benzyl-3-bromo-4-(2-phenylethyl)pyridin- 2(iH)-one. A mixture of l-benzyl-3-bromo-4-(phenylethynyl)pyridin2(IH)-one (0.3 g), and platinum oxide (0.05 g) in a solvent mixture of EtOAc (i0.0 mL) and EtOH ( i0.0 mL) was stirred in an atmosphere of hydrogen at 15 psi in a Fischer porter bottle for 45 min. The catalyst was removed by filtration, and filtrate was concentrated. The resulting residue was purified by silica gel flash chromatography using 25% EtOAc in hexanes as the eluent. The appropriate fractions (visualized under an UV lamp) were combined and concentrated under reduced pressure. IHNMR (CD OD) 6: 7.56 (d, IH, J = 6.8 Hz), 7.31 - 7.17 (m, i0 H), 6.24 (d, IH, J = 6.8 Hz), 5.19 (s, 2H), 2.96 (m, 2H) , and 2.91 (m, 2H) ; ES-MS m/z = 368 (MH÷) ; HR-MS m/z (MH÷) calcd C 20 HIgNOBr 368.0650, found 368.0630. Example 53 3-bromo-l-(3-fluorobenzyl)-6-methyl-4-(2phenylethyl)pyridin-2(iH)-one The title compound was prepared essentially according to the procedure of Example 52. IHNMR 6: (CD 3 OD) 6: 7.35 (m, IH), 7.31-7.16 (m, 5H), 6.99(m, IH), 6.91 (m, IH), 6.81 (m, IH), 6.20 (s, IH) , 5.41 (s, 2H) , 2.94 (m, 4H) , and 2.24 (s, 3H) ; 19F-NMR (CD 3 OD) 6: -115.01 (m) ; ES-MS, m/z = 400 (MH÷) ; HR-MS m/z calcd C 21 H 20 NOBrF 400.0712, found 400.0695. Example 54 4-(benzyloxy)-3-bromo-l-(2,6-dichlorophenyl)-6methylpyridin-2(IH)-one O ¢l Gl Step A Preparation of 3-acetyl-l-(2,6-dichlorophenyl)-4-hydroxy6-methylpyridin-2(iH)-one A mixture of 2,6 dichlorophenylisocyanate (4.8 g, 0.025 mol), and diketene (4.3 g, 0.05 mol) in toluene (15.0 mL) was heated to reflux for 4 h under an atmosphere of argon. After removal of the solvent in vacuo, the residue was purified by silica gel flash chromatography using EtOAc/hexanes (1:3 v/v) . The appropriate fractions, as monitored by ES mass spectrometry (MH m/z = 312) were combined and concentrated under reduced pressure. The resulting yellow solid (2.3 g) was further purified by reverse-phase HPLC using 10-90% acetonitrile/water gradient (45 min) at a flow rate of I00 mL/min. The appropriate fractions, as monitored by ES mass spectrometry (MH ÷ m/z = 312) were combined and concentrated to half the volume. The solid that separated was extracted with EtOAc ( 2 x 25 mL) . The combined extracts were washed with water, dried (Na 2 S0 4 ), filtered, and concentrated to dryness to give the title compound (0.77 g) as a pale yellow powder: IHN-MR (CD 3 OD) 6:7.62 (m, 2H), 7.52 (m, IH) , 6.19 (s, IH) , 2.59 (s, 3H) , and 1.96 (s, 3H) ; ES-MS m/z = 312 (MH÷) ; HR-MS, m/z calc C 14 HI 2 N0 3 CI 2 312.0189, found 312.0214. Step B. Preparation of 1-(2,6-dichlorophenyl)-4-hydroxy-6methylpyridin-2(iH)-one OH CJ ¢I A mixture of 3-acetyl-l- (2,6-dichlorophenyl)-4-hydroxy-6methylpyridin-2 (IH)-one 0.7 g (0.002tool) in n-butanol (3.0 niL) containing sulfuric acid (1.5 mL) was heated at 120 °C for 4 h. The dark reaction mixture was cooled, added ice/water (25 mL), and extracted with EtOAc (2 x 25 ml). The combined organic extracts were washed with water, dried (Na 2 SO 4 ), filtered, concentrated under reduced pressure and the resulting material was purified by silica gel flash chromatography using 25% EtOAc in hexanes as the eluent to afford the title compound (0.14 g) as a pale yellow powder: HNMR (CD3OD) 6:7.6 (m, 2H), 7.48 (m, IH), 6.10 (dd, IH), 5.78 (d, IH, J = 2.4 Hz), 1.91 (s, 3H) ; ES-MS m/z = 270 (MH÷ ) ; HRMS, m/z calc C 12 HI 0 NO 2 CI 2 270.0083, found 270.0103. Step C Preparation of 4-(benzyloxy)-l-(2,6-dichlorophenyl)-6methylpyridin-2(IH)-one C CL Ci A mixture of i- (2,6-dichlorophenyl) -4-hydroxy6- methylpyridin-2 (IH) -one (0.125 g, 0.46 mmol) and benzylbromide (0.I mL) in DMF (2.5 mL) was stirred at room temperature for 16 h. The reaction mixture was diluted with water (i0.0 mL) and extracted with EtOAc (2 x 20 mL) . The combined organic extracts were washed with water, dried (Na 2 SO 4), filtered, concentrated under reduced pressure and the resulting material was purified by silica gel flash chromatography using 25% EtOAc in hexanes to afford the title compound (0.II g) as a pale yellow syrup: IHNMR (CD 3 OD) 6: m/z=360 (MH÷) ; HR-MS, m/z calc C 19 HI 6 N0 2 CI 2 , 360.0553, found 360.0569. Step D Preparation of 4-(benzyloxy)-3-bromo-l-(2,6dichlorophenyl)-6-methylpyridin-2(iH)-one A mixture of 4-(benzyloxy)-l-(2,6-dichlorophenyl)-6methylpyridin-2(iH)-one ( 0.i g, 0.278 mmol) and Nbromosuccinimide (0.055 g, 0.3 mmol) in dichloroethane (3.0 mL) was stirred at room temperature for 1 h, and heated at °C under argon for 30 min. The reaction mixture was then diluted with dichloroethane (15 mL), washed with water, dried (Na 2 S0 4), filtered, and concentrated under reduced pressure. H NMR (CD 3 OD) 6: 7.64 (m, 2H), 7.55 (m, 3H), 7.38 (m, 3H), 6.65 (s, IH), 5.34 (s, 2H), and 2.00(s, 3H) ; ES-MS m/z = 439 (MH÷ ); HR-MS, m/z calc C 19 HI 6 NO 2 CI 2 Br, 439.9635, found 439.9669. Example 3-bromo-l-(3-fluorobenzyl)-4-(2-phenylethyl)pyridin2(IH)-one Br The title compound was prepared essentially according to the procedure of Example 52. IHNMR (CD 3 OD) 6: 7.58 (d, IH, J = 6.8 Hz), 7.4-7.0 (m, 9H), 6.26 (d, IH. J = 6.8 Hz), 5.19 (s, 2H), 2.97 (m, 2H), and 2.90 (m, 2H) ; ES-MS m/z = 386 (MH÷) ; HRMS, m/z calc C 20 H sNOFBr, 386.0550, found 386.0585. Example 56 l-benzyl-3-bromo-2-oxo-l,2-dihydropyridin-4-yl methyl(phenyl carbamate O I'N-- Step A Preparation of l-benzyl-2-oxo-l,2-dihydropyridin~4-yl methyl(phenyl)carbamate O j/NO To a chilled solution of l-benzyi-4-hydroxypyridin-2(iH)- one (0.375 g, 1.86 mmol) in anhydrous acetonitrile (i0 mL) was added triethylamine (0.206 g, 2.04 mmol) followed by N-methylN-phenylcarbamoyl chloride (0.379 g, 2.24 mmol) . The reaction mixture was stirred under nitrogen atmosphere at 0°C for min then at room temperature for lh. The reaction was monitored by TLC (5% methanol in dichloromethane). The solvent was removed under reduced pressure and the residue was washed with 10% citric acid and extracted with EtOAc. The organic extracts were combined, washed with water dried over anhydrous Na 2 S0 4 , and filtered. The solvent was removed under reduced pressure to afford a yellow syrup. The residue was purified by flash chromatography (silica gel) using 5% Me0H in CH 2 C1 2 to give the desired product (0.382g, 61%) as a white semisolid. MS and IH-NMR were consistent with the desired structure. IH-NMR (d 6 -DMSO, 400 MHz) 6: 7.8 (d, IH) , 7.39 (m, 10H) , 6.19 (s, 2H), 5.03 (s, 2H), 3.29 (s, 3H) ; HR-MS (ES) m/z calcd for C 20 HIBN 2 0 3 (MH÷)= 335.1396, observed 335.1418. Step B l-benzyl-3-bromo-2-oxo-l,2-dihydropyridin-4-yl methyl (phenyl) carbamate To a solution of !-benzyl-2-oxo-l,2-dihydropyridin-4-yl methyl (phenyl) carbamate (0.38 g, 1.13 mmol) in anhydrous CH 2 C1 2 (7 mL) was added N-Bromosuccinimide (NBS, 0.24 g, 1.34 mmol). The reaction was stirred overnight at room temperature under nitrogen atmosphere. The reaction mixture was purified by flash chromatography (silica gel) using EtOAc/hexanes (i:I v/v). The appropriate fractions were collected according to ES MS (M+H 413) and concentrated. The dried product showed about 14% of di-brominated product by analytical HPLC. The compounds were separated by reverse phase HPLC using a 10-90% acetonitrile in water, 30 min gradient at a i00 mL/min flow rate, to afford (after lyophilization) the salt of the desired compound. The salt was diluted in EtOAc and washed with NaHCO 3. The organic extracts were dried over anhydrous Na 2 SO 4 , filtered, and concentrated to afford the desired compound (0.271 g, 58%) as a beige solid. MS and H-NMR were consistent with the desired structure. IH-NMR (d 6 -DMSO, 400Hz) 6: 7.83 (d, IH) , 7.39 (m, 10H), 6.48 (s, IH), 5.12 (s,2H) , 3.33 (s, 3H) ; HR-MS (ES) m/z calcd for C 20 HI O Br (MH÷)= 413.0495, observed 413.0496. Example 57 4- (benzyloxy) -3-ethynyl-l- (3fluorobenzyl) pyridin-2 (IH) - one O Step A Preparation of 4÷(benzyloxy)-l-(3-fluorobenzyl)-3iodopyridin-2(1H)-one Heated a reaction mixture of 4-(benzyloxy)-l-(3fluorobenzyl)pyridin-2(!H)~one (4.83 g, 15.6 mmol) in anhydrous acetonitrile (55 mL) and N-iodosuccinimide (NIS, 3.86 g, 17.1 mmol) under nitrogen atmosphere at 65° C for 4 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (silica gel) using EtOAc/hexanes (i:I v:v). The appropriate fractions were collected according to ES MS (M+H 436) and washed with Na 2 SO 3 to remove the color impurities. The fractions were concentrated under reduced pressure and dried in vacuo to afford the desired product (6.15 g, 90%) as a light yellow solid. MS and IH-NMR were consistent with the desired structure. IH-NMR (CD 3 OD, 400Hz) 6: 7.73 (d, IH) , 7.47 (d, 2H) , 7.39 (m, 4H) , 7.08 (m, 3H) , 6.39 (d, IH) , 5.29 (s, 2H) , 5.19 (s, 2H) ; HR-MS (ES) m/z calcd for C 19 HIsNO 2 FI (MH÷)= 436.0210, observed 436.0196. Step B Preparation of 4- [ (trimethylsilyl) ethynyl ] pyridin-2 i (benzyloxy) -i- (3fluorobenzyl) - 3- (IH) -one TMS F --O-- jN Degassed a solution of 4- (benzyloxy)-l- (3-fluorobenzyl)- 3 -iodopyridin-2 (IH) -one (2.01 g, 4.62 mmol) in anhydrous acetonitrile (25 mL) under argon atmosphere. Triethylamine (i. II g, ii mmol) was added and quickly degassed. The reaction mixture was chilled in an ice bath for 15 minutes before adding bistriphenylphosphine-palladium chloride (0.34 g, 0.48 mmol) and cuprous iodide (0.2 g). The reaction was stirred at room temperature for 30 min before heating at 60° C under an atmosphere of argon for 2 h. The reaction mixture was filtered through a bed of celite and the filtrate was concentrated under reduced pressure. The dark brown residue was diluted with CH 2 C1 2 (i00 mL) and washed with water. The organic extracts were combined, dried over anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure. The dark brown residue was purified by flash chromatography (silica gel) using 30% EtOAc in hexane. The appropriate fractions were combined and concentrated under reduced pressure to afford the desired product (1.34 g, 72%) as a light yellow solid. MS and IH-NMR were consistent with the desired structure. IH-NMR (CD 3 OD, 400Hz) 5: 7.74 (d, IH), 7.47 (d, 2H), 7.35 (m, 4H) , 7.09 (m, 3H) , 6.46 (d, IH) , 5.26 (S, 2H), 5.13 (s, 2H) , 0.18 (s, 9H); HR-MS (ES) m/z calcd for C 24 H 24 NO 2 FSi (MH÷)= 406.1638, observed 406.1610. Step C Preparation of fluorobenzyl)pyridin2(iH)_ 4-(benzyloxy)-3-ethynyl1_( 3_ 0 ne cH To a solution of 4-(benzyloxy)-l-(3-flu 0 r 0 benzyl)_ 3 _ [(trimethylsilyl)ethynyl]pyridin_ 2(iH)_ 0 ne (1.31 g, 3.2 mmol) in anhydrous acetonitrile (25 mL) at 0° C was added tetrabutylammonium fluoride (0.611g, 1.93 mmol). The reaction was stirred at 0 o C for 15 min then for 1 h at room temperature. The reaction was concentrated under reduced pressure and the residue was diluted with EtOAc and washed with water. The organic extracts were combined, dried over anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel) using EtOAc in hexanes (I:i v/v) . The appropriate fractions were combined and concentrated under reduced pressure to afford the desired product (0.779 g, 72%) gold solid. MS and IH-NMR were consistent with the desired structure. IH-NMR (CD 3 OD, 400Hz) 6: 7.73 (d, IH) , 7.43 (d, 2H) , 7.35 (m,4H), 7.09 (m,3H) , 6.45 (d, IH) , 5.27 (s, 2H) , 5.13 (s,2H) , 3.78 (s, IH) ; HR-MS (ES) m/z calcd for C 21 H NO 2 F (MH÷) = 334.1243, observed 334.1234. Example 58 4-(benzylamino)-3-bromo-l-(3-fluorobenzyl)pyridin-2(iH)- one NH ,Br Step A Preparation of l-(3-fluorobenzyl)-4-hydroxypyridin-2(iH)- one HO 0 F In a Fischer-Porter bottle, added a solution of 4- (benzyloxy)-l- (3-fluorobenzyl)pyridin-2 (iH)-one (4.5 g, 14.56 mmol) in absolute ethano! (20 mL). Flushed the solution with nitrogen then added palladium catalyst (1.05 g) . Sealed bottle and evacuated system. The system was purged with hydrogen gas (2 X 15 psi) to check for leaks. The reaction was charged with hydrogen (35 psi) and stirred at room temperature for 45 min. The system was evacuated and flushed with nitrogen. The reaction was filtered and the catalyst was carefully washed with fresh ethanol. The filtrate was concentrated under reduced pressure. MS and IH-NMR were consistent with the desired structure. IH-NMR (CD 3 OD, 400Hz) 6: 7.54 (d, !H) , 7.32 (m, IH) , 7.06 (m, 3H), 6.05 (dd, IH), 5.83 (s, IH), 5.09 (s, 2H); HR-MS (ES) m/z calcd for C 12 HI 0 NO 2 F (MH÷)= 220.0774, observed 220.0787. Step B Preparation of 4-(benzylamino)-l-(3-fluorobenzyl)pyridin2(IH)-one Heated a reaction mixture of 1-(3-fluorobenzy!)-4hydroxsrpyridin-2(1H)-one (1.005 g, 4.5 mmol) in benzylamine (15 mL) at reflux (185° ¢) under nitrogen atmosphere for 24 h. The reaction was monitored by ES-MS (MH+ 309). The solvent was removed by vacuum distillation to give a yellow residue. MS and IH-NMR were consistent with the desired structure. IH-NMR (CD 3 OD, 400Hz) 6:7.31 (m, 7H), 7.03 (m, 3H), 5.98 (dd, IH), 5.45 (s, IH), 5.00 (s, 2H), 4.30 (s, 2H) ; HR-MS (ES) m/z calcd for C 19 HIvN 2 OF (MH÷)= 309.1403, observed 309.1375. Step C Preparation of fluorobenzyl ) pyridin-2 (IH) 4-(benzylamino)-3-bromo-l-(3- -one To a solution fluorobenzyl)pyridin-2(iH)-one anhydrous CH 2 C1 2 (i0 mL) 0.30 g, 1.7 mmol). The of 4-(benzylamino)-l- (3- (0.50 g, 1.62 mmol) in was added N-bromosuccinimide (NBS, reaction was stirred at. room temperature under a nitrogen atmosphere for 3 h. The reaction mixture was purified by flash chromatography (silica gel) using EtOAc in hexanes (i:i v/v) . The appropriate fractions were combined and concentrated. MS and IH-NMR were consistent with the desired structure. IH-NMR (CD 3 OD, 400Hz) 5: 7.41 (d, IH) , 7.31 (m, 6H), 7.04 (m, 3H), 5.99 (d, IH), 5.08 (s, 2H), 4.53 (s, 2H); HR-MS (ES) m/z calcd for CIgHI 6 N 2 OFBr (MH÷)= 387.0508, observed 387.0504. Example 59 F 3-Bromo-l-cyclopropylmethyl-4-(4-fluorobenzyloxy)- iH-pyridin-2-one Step i. Preparation of 4-[(4-Fluorobenzyloxy]pyridine-loxide. To an ice-cold solution of sodium hydride (1.9 g, of a 60% dispersion in mineral oil, 46 mmol) in DMF (39 mL) was added 4-fluorobenzyl alcohol (5.1 mL, 46 mmol). The reaction mixture was warmed to room temperature, 4-chloropyridine-loxide I (5.0 g, 39 mmol) was added, and the reaction mixture was stirred for 6 h. The reaction mixture was diluted with a 50% aqueous solution of brine, and extracted with CHCI 3 (7 x mL) . The combined organics were dried (MgSO 4 ), filtered, and concentrated under reduced pressure. Trituration with Et 2 0 afforded 4-[(4-fluorobenzyloxy]pyridine-l-oxide as an offwhite solid (9.1 g, 90%), which was used in the next step without further purification or characterization. Step 2. Preparation of 4-(4-Fluorobenzyloxy)-iH-pyridin-2one. A solution of 4-[(4-fluorobenzyloxy]pyridine-l-oxide (6.4 g, 29 mmol) in acetic anhydride (97 mL) was heated at reflux for 3 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The residue was diluted with I:i MeOH/water (34 mL), and the mixture was stirred at room temperature for 1 h. The solvent was removed under reduced pressure. Trituration with Et 2 0/hexanes afforded 4-(4-fluorobenzyloxy)-IH-pyridin-2-one as a brown solid (3.1 g, 48%): IH NMR (300 MHz, CDCI 3 ) 8 7.40-7.36 (m, 2H) , 7.22 (d, J = 8 Hz, IH), 7.09 (t, J = 7 Hz, 2H), 6.03 (dd, J = 7, 3 Hz, IH), 5.94 (d, J = 3 Hz, IH), 4.98 (s, 2H) . Step 3. Preparation of 3-Bromo-4-(4-fluorobenzyloxy)-iHpyridin-2-one. To an ice-cold solution of 4-(4-fluorobenzyloxy)pyridine2(iH)-one (3.1 g, 14 mmol) in AcOH (26 mL) was added a solution of bromine (0.79 mL, 15 mmol) in AcOH (51 mL), and the reaction mixture was stirred at room temperature for 2 h. The solvent was removed under reduced pressure, and purification by flash column chromatography (silica, i:i Et 2 0/hexanes) to afford 3-bromo-4-(4-fluorobenzyloxy)-IHpyridin-2-one as an orange solid (0.78 g, 48%): MS APCI m/z 298 [M + H]* Step 4. Preparation of 3-Bromo-l-cyclopropylmethyl-4-(4fluorobenzyloxy)-iH-pyridin-2-one. To a solution of 3-bromo-4-(4-fluorobenzyloxy)-iH-pyridin-2one (0.25 g, 0.84 mmol) in DMF (13 mL) was added K 2 C0 3 (0.33 g, 1.7 mmol) and cyclopropylmethyl bromide (0.14 g, 1.0 mmol), and the reaction mixture was stirred at ii0 °C for 2 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was diluted with a 50% aqueous solution of brine, and extracted with CHCI 3 (3 x 50 mL). The combined organics were washed with water and then brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, I:i EtOAc/hexanes) afforded 3-bromo-lcyclopropyl-methyl-4- (4fluorobenzyloxy) - IH-pyridin-2-one as a yellow solid (0.12 g, 39%): mp 139-141 °C; IH NMR (300 MHz, CDCI 3) 6 7.43-7.34 (m, 3H), 7.07 (t, J = 9 Hz, 2H), 6.06 (d, J = 6 Hz, IH) , 5.19 (s, 2H), 3.82 (d, J = 9 Hz, 2H) , 1.26-1.23 (m, IH), 0.62-0.57 (m, 2H), 0.40-0.36 (m, 2H). ESHRMS m/z 352.0368 (M+H C 16 HI 6 BrFNO 2 requires 352.0343) Examples 60-69 F- BrO N R O The compounds of Examples 60-69 are prepared essentially according to the procedures set forth above for Example 59. Example No. R Ex. 60 pyridin-4-ylmethy1 Ex. 61 pyridin-3-ylmethyl Ex. 62 4-terc-butylbenzyl Ex. 63 3-trifluoromethyibenzyl M+H ESHRMS MF Requires m/z C 18 HI 4 BrFN 2 0 2 489.0296 489. 0281 C 2 H 2 BrFNO 2 444.0969 444. 0971 C 20 HI 4 BrF 4 NO 2 456.0217 456. 0202 Ex. 64 Biphenyl-2-ylmethyl Z 2 sHI BrFNO 2 Ex. 65 4-methoxybenzyl Z 20 HITBrFNO] Ex. 66 4-cyanobenzyl S 20 HI 4 BrFN 2 0 2 Ex. 67 4-trifluoromethylbenzyl C 20 HI 4 BrF 4 N0 2 'Ex. 68 Biphenyl-4-ylmethyl C 2 sHIgBrFNO 2 Ex. 69 cyclohexylmethyl C 19 HnBrFN0 2394 NMR characterization of compounds of Examples Ex. NO. NMR Data *H NMR (300 MHz, CDCI 3 ) 6 8.57 (dd, J = 6, Ex. (m, 2H), 7.16 (d, J = 6 Hz, 2H), 7.09 (t, (d, J = 6 Hz, IH), 5.20 (s, 2H), 5.16 (s, 2}{) Ex. 61 IH NMR (300 MHz, CDCI ) 6 8.58-8.55 (m, 2H), IH) , 7.41-7.37 (m, 2H) , 7.31-7.26 (m, 2H), 5.17 (d, J = 6 Hz, IH), 5.18 (s, 2H), 5.16 Ex. 62 IH NMR (300 MHz, MeOD) 6 7.75 (d, IH, J -- Hz, 2H) , 7.37 (d, J = 9 Hz, 2H) , 7.22 (d, 6.99 (m, 2H), 6.52 (d, J = 9 Hz, IH) , 5.29 2H), 1.28 (s, 9H) Ex. 63*H NMR (300 MHz, CDCI 3 ) 6 7.58-7.37 (m, 5H) 7.08 (t, J = 7 Hz, 2H), 6.10 (d, J = 7 Hz, 5.18 (s, 2H) Ex. 64 IH NMR (300 MHz, CDCI 3 ) 7.42-7.27 (m, IIH), 2H) , 6.72 (d, J = 7 Hz, IH) , 5.88 (d, J = 2H), 5.12 (s, 2H) Ex. 65 IH NMR (300 MHz, CDCI ) 6 7.38-7.36 (m, 2H), 7.08 (s, 2H), 6.86 (d, J = 7 Hz, 2H), 6.01 5.15 (s, 2H), 5.09 (s, 2H), 3.78 (s, 3H) Ex. 66 IH NMR (300 MHz, CDCI 3 ) 6 7.64-7.61 (m, 2H) 7.27-7.25 (m, IH), 7.12-7.06 (m, 2H), 6.11 5.19 (s, 4}{) Ex. 67 H NMR (300 MHz, CDCI ) 6 7.59 (d, J = 6 Hz, 4H) , 7.29-7.25 (m, IH), 7.08 (t, J = 6 Hz, Hz, IH), 5.20 (s, 2}{), 5.18 (s, 2H) Ex. 68 IH NMR (300 MHz, CDCI 3 ) 6 7.57-7.54 (m, 7H), 7.30-7.26 (m, IH), 7.08 (t, 6.06 (d, J = 6 Hz, IH), 5.20 (s, 2H), Ex. 69 IH NMR (300 MHz, CDCI ) 6 7.93 (d, J = 6 Hz, 2H), 7.29-7.26 (m, IH), 7.09 (t, J = 9 Hz, Hz, IH) , 5.17 (s, 2H) , 4.14 (d, J = 6 Hz, 5H) , 1.32-1.05 (m, 5H) Example { 3- [3-Bromo-4- (4fluorobenzyloxy) -2-oxo-2H-pyridinl- ylmethyl]benzyl}carbamic acid tert-butyl ester Step i. Preparation of 3-Hydroxymethylbenzonitrile. To an ice-cold solution of 3-cyanobenzaldehyde (5.0 g, 38 mmol) in i:i MeOH/THF (90 mL) was added NaBH 4 (1.6 g, 42 mmol), and the reaction mixture was stirred for 3 h. The reaction mixture was diluted with brine, and the solvent was removed under reduced pressure. The residue was dissolved in water, and the aqueous layer was extracted with Et 2 0 (3 x i00 mL). The combined organics were washed with brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure to provide 3-hydroxymethyl-benzonitrile (4.95 g, 98%) as a clear oil, which was used in the next step without further purification or characterization. Step 2. Preparation of 3-(tertButyldimethylsilyloxymethyl)benzonitrile. To an ice-cold solution of 3-hydroxymethyl benzonitrile (4.95 g, 37 mmol) in CH 2 C1 2 (47 mL) was added imidazole (5.1 g, 74 mmol), DMAP (0.45 g, 3.7 mmol), and TBSCI (6.2 g, 41 mmol), and the reaction mixture was stirred for 12 h. The reaction mixture was diluted with water, and the aqueous layer was extracted with CH 2 C1 2 (3 x 150 mL). The combined organics were washed with brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure to provide 3°(ter - butyldimethylsilyloxymeth l)-benzonitrile (9.1 99%) as a clear oil: IH NMR (300 MHz, CDCI 3 ) 6 7.51 (s, IH), 7.42 (d, J 6 Hz, IH), 7.35-7.28 (m, IH), 4.75 (s, 2H), 0.94 (s, 9H), 0.ii (s, 6H)° Step 3. Preparation of 3-(tertButyldimethylsilyloxymethyl)benz¥1amine. To an ice-cold solution of 3-(tertbutyldimethylsilyloxymethyl)benzonitrile (4.5 g, 18 mmol) in THF (47 mL) was added LiAIH 4 (27 mL, of a 1 M solution in THF, 27 mmol), and the reaction mixture was stirred at reflux for 3 h. The reaction mixture was cooled to 0 °C, and the reaction was quenched with water (25 mL) and 15%NaOH in water (75 mL) . The reaction mixture was filtered, concentrated under reduced pressure, and the residue was dissolved in EtOAc. The organic solution was washed with water and then brine, dried (MgS0 4 ), filtered, and concentrated under reduced pressure to provide 3- (tert-Butyldimethylsilyloxymethyl)benzylamine (1.4 g, 30%) as a clear oil: iH N-MR (300 MHz, CDCI 3 ) 6 7.22-7.10 (m, 4H), 4.57 (s, 2H), 3.74 (s, 2H) , 0.84 (s, 9H), 0.09 (s, 6H) . Step 4. Preparation of 3-(Hydroxymethyl)benzylcarbamic acid tert-butyl ester. To a solution of 3-(tertbutyldimethylsilyloxymethyl)benzylamine (1.4 g, 5.5 mmol) and Et 3 N (1.5 nIL, Ii mmol) in CHIC1 2 (28 mL) was added di-tertbutyl dicarbonate (1.3 g, 5.8 mmol), and the reaction mixture was stirred for 12 h. The reaction mixture was diluted with water and extracted with CH 2 C1 2 (3 x i00 mL). The combined organics were washed with brine, dried (MgS0 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, CH 2 C1 2 ) to afford 3- (hydroxymethyl)benzylcarbamic acid tert-buty ester as a Step 5. Preparation of 3-(Bromomethyl)benzylcarbamic acid tert-butyl ester. To an ice-cold solution of 3- (hydroxymethylbenzyl)carbamic acid tert-butyl ester (0.7 g, 3.0 mmol) and CBr 4 (I.0 g, 3.1 mmol) in THF (14 mL) was added Ph P (0.81 g, 3.1 mmol), and the reaction mixture was stirred for 18 h. The reaction mixture was filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 5:95 to15:85 EtOAc/hexanes) to afford the 3-(bromomethyl)benzyl-carbamic acid tert-butyl ester as a white solid (0.42 g, 51%): IH NMR (300 MHz, MeOD) 6 7.55 (s, IH) , 7.32-7.27 (m, 2H) , 7.21-7.19 (m, IH) , 4.54 (s, 2H), 4.21 (s, 2H), 1.28 (s, 9H) . Step 6. Preparation of l{3-[3-Bromo-4-(4-fluorobenzyloxy)-2oxo-2H-pyridin-l-ylmethyl]benzyl}carbamic acid tert-butyl ester. To a solution of 3-bromo-4- (4-fluorobenzyloxy)pyridine-2(IH)- one (from Step 3, synthesis EXAMPLE 59 ) (0.2 g, 0.67 mmol) in DMF (II mL) was added K 2 CO 3 (0.26 g, 1.3 mmol) and 3- (bromomethyl)benzylcarbamic acid tert-butyl ester (0.23 g, 0.80 mmol), and the reaction mixture was stirred at 80 °C for 3 hours. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was diluted with a 50% aqueous solution of brine (24 mL), and extracted with CHCI 3 (4 x 50 mL) . The combined organics was washed water and then brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 3:7 EtOAc/hexanes) and f luorobenzyloxy) -2 - oxo2H-pyridin1 -ylmethyl ] benzyl } carbamic acid tert-butyl ester as an off-white solid (0.07 g, 20%): mp 136-138 °C; IH NMR (300 MHz, CDCI 3 ) 6 7.42-7.37 (m, 2H), 7.307.20 (m, 5H), 7.08 (t, J = 9 Hz, 2H), 6.04 (d, J = 9 Hz, IH), 5.16 (s, 2H), 5.14 (s, 2H), 4.28 (d, J = 6 Hz, IH), 1.44 (s, 9H) . ESHRMS m/z 517.1124 (M+H C 2 sH 27 BrFN 2 0 4 requires 517.1133) Example 71 F l-(3-Aminomethylbenzyl)-3-bromo-4-(4-fluorobenzyloxy)-IHpyridin-2-one To an ice-cold solution of i-[3-{N-tertBut oxycarbonyl } aminome thylbenzyl ] - 3 - bromo - 4 - ( 4 - fluorobenzyloxy)pyridine-2 (iH)-one (Example 69) (0.05 g, 0.i mmol) in CH 2 C1 2 (2 mL) was added TFA (2 mL), and the reaction mixture was stirred for 1 h. The solvent was removed under reduced pressure to provide i- (3-aminomethylbenzyl)-3-bromo-4- (4-fluorobenzyloxy)-IH-pyridin-2-one as a tan solid (0.049 g, i00%), as the TFA salt: mp 127-139 °C; IH NMR (300 MHz, DMSOd 6) 6 8.13 (br s, 2H), 7.94 (d, J = 6 Hz, IH), 7.52-7.47 (m, 2H), 7.44-7.37 (m, 2H), 7.27 (t, J = 8 Hz, 3H), 6.53 (d, J = 8 Hz, IH) , 5.30 (s, 2H) , 5.14 (s, 2H) , 4.01 (d, J = 6 Hz, 2H) , 3.39 (br s, 2H) ; Anal. Calcd for C 20 HI BrF 2 N 2 0 2 -1.125 TFA: C, 48.99; H, 3.53; N, 5.13. Found: C, 48.80; H, 3.43; N, 4.75. ESHRMS m/z 417.0608 (M+H C 20 HIgBrFN 2 0 2 requires 417.0609). Example 72 F 0 C0 2 Me Methyl 2-[3-Bromo-4-(4-fluorobenzyloxy)-2-oxo-2H-pyridin-lylmethyl]benzoate The title compound was prepared by a procedure similar to one described for EXAMPLE 59 (0.36 g, 48%): mp 161-165 °C; NMR (300 MHz, CDCI ) 6 7.98 (d, J = 6 Hz, IH), 7.51-7.26 (m, 6H), 7.11-7.05 (m, 2H), 6.05 (d, J = 8 Hz, IH), 5.60 (s, 2H), 5.18 (s, 2H), 3.93 (s, 3H) . ESHRMS m/z 446.0430 (M+H C 21 HIsBrFNO 4 requires 418.0398) Example 73 Br°O 0 < OH 3 - Bromo4 - ( 4 - f luorobenzyloxy) - 1 - (2 - hydroxymet hylbenzyl IH-pyridin2 -one To an ice-cold solution of 3-bromo-4-(4-fluorobenzyloxy)-l-(2hydroxymethylbenzyl)-iH-pyridin-2-one (Example 72) (0.25 g, 0.56 mmol) in THF (I mL) was added LiBH 4 (2.0 M solution in THF, 0.56 mmol), and the reaction mixture was stirred at for 6 hours. The reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was dissolved in EtOAc. The organic solution was washed with brine, dried (MgSO 4 ), filtered, and concemtrated under reduced pressure. IH NMR (300 MHz, DMS0-d 6 6 7.82 (d, J = 8 Hz, IH), 7.54-7.49 (m, 2H), 7.41 (d, J = 7 Hz, IH), 7.29-7.21 (m, 4H), 6.81 (d, J = 7 Hz, IH), 6.53 (d, = 8 Hz, IH), 5.30-5.25 (m, 3H), 5.18 (s, 2H), 4.60 (d, J = 7 Hz, 2H) . ESHRMS m/z 418.0437 (M+H C 20 HIsBrFN0 3 requires 418.0449) Example 74 F 0 " y/X.N / 3-Bromo-4-(2,4-difluorobenzyloxy)-l- [(4dimethylaminomethyl)benzyl]-iH-pyridin-2-one Step i. Preparation of 4-(2,4-Difluorobenzyloxy)pyridine-1oxide. To an ice-cold solution of sodium hydride (1.2 g of a 60% dispersion in mineral oil, 51 mmol) in DMF (43 mL) was added 2,4-difluorobenzyl alcohol (5.7 mL, 51 mmol). The reaction mixture was warmed to room temperature, 4-chloropyridine-loxide I (5.5 g, 43 mmol) was added, and the reaction mixture was stirred for 6 h. The reaction mixture was diluted with a 50% aqueous solution of brine, and extracted with CHCI 3 (7 x mL). The combined organics were dried (MgSO 4 ), filtered, and the solvent was removed under reduced pressure. Trituration with Et 2 0 afforded 4-(2,4-difluorobenzyloxy)pyridine~l-oxide as Step 2. Preparation of 4-(2,4-Difluorobenzyloxy)-IH-pyridin o 2-one. A solution of 4-(2,4-difluorobenzyloxy)pyridine-l-oxide (13.4 g, 57 mmol) in acetic anhydride (30 mL) was stirred at reflux for 4 h. The solvent was removed under reduced pressure, the residue was diluted with I:I MeOH/water (60 mL), and the mixture was stirred at room temperature for 1 h° The solvent was removed under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 9:1 methylene chloride/methanol) provided 4-(2,4difluorobenzyloxy)-iH-pyridin-2-one as a light brown solid (4.2 g, 31%): IH NMR (300 MHz, CDCI 3 ) 6 7.43 (q, J = 8 Hz, IH), 7.23 (d, J = 7 Hz, IH), 6.91-6.87 (m, 2H), 6.02 (dd, J = 8, 2 Hz, IH) , 5.97 (d, J = 2 Hz, IH), 5.03 (s, 2H) . Step 3. Preparation of 3-Bromo-4-(2,4-difluorobenzyloxy)-iH- pyridin-2-one. To an ice-cold solution of 4-(2,4-difluorobenzyloxy)-iHpyridin-2-one (0.75 g, 3.1 mmol) in AcOH (12 mL) was added a solution of bromine (0.2 mL, 3.5 mmol) in AcOH (6 mL), and the reaction mixture was stirred I0 min. The solvent was removed under reduced pressure to afford 3-bromo-4-(2,4difluorobenzyloxy)-iH-pyridin-2-one as a white solid (I.0 g, 100%): ESI MS m/z 299 [M + HI÷ Step 4. Preparation of 3-Bromo-l-(4-chloromethylbenzyl)-4- (2,4-difluorobenzyloxy)-IH-pyridin-2-one. To a solution of 3-bromo-4-(2,4-difluorobenzyloxy}-iH-pyridin2-one (0.60 g, 2.5 retool) in DMF (40 mL) was added K 2 CO 3 (0.70 g, 5.1 retool) and -dichloro-p-xylene (0.53 g, 3.0 retool), and the reaction mixture was stirred at ii0 °C for 2 h. The reaction mixture was cooled to room temperature, diluted with brine, and extracted with CHCI 3 (4 x I00 mL). The combined organics were washed water and then brine, dried (Na 2 SO 4 ), filtered, and concentrated under reduced pressure to afford 3bromo-l- (4-chloromethylbenzyl) -4- (2,4-difluorobenzyloxy) -IHpyridin-2-one as an off-white solid (0.49 g, 43%) : iH NMR (300 MHz, CDCI ) 6 7.54 (app q, J = 8 Hz, IH), 7.38-7.28 (m, 5H), 6.94 (td, J = 8, 2 Hz, IH), 6.85 (td, J = 8, 2 Hz, IH), 6.10 (d, J = 9 Hz, IH), 5.21 (s, 2H), 5.16 (s, 2H), 4.56 (s, 2H) . Step 5. Preparation of 3-Bromo-4-(2,4-difluorobenzyloxy)-l- [(4-dimethylaminomethyl) benzyl]-iH-pyridin-2-one. To a sealed tube containing 3-bromo-l-(4-chloromethylbenzyl)- 4-(2,4-difluoro-benzyloxy)-IH-pyridin-2-one (0.49 g, I.i mmol) was added a solution of dimethylamine (5.5 mL of a 2.0 M solution in THF, II mmol), and the reaction mixture was stirred for 15 h. The solvent was removed under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 92:7.2:0.8 methylene chloride/methanol/ammonia) provided 3-bromo-4-(2,4difluorobenzyloxy)-l-(4-dimethylaminomethylbenzyl)-iH-pyridin2-one as a light yellow solid (0.23 g, 46%) : mp ii1-I13 °C; IH NMR (500 MHz, CDCI 3 ) b 7.50-7.49 (m, IH), 7.26-7.22 (m, 5H), 6.90-6.88 (m, IH), 6.82-6.78 (m, IH), 6.04 (d, J = 6 Hz, IH), 5.16 (s, 2H), 5.11 (s, 2H), 3.37 (s, 2H), 2.19 (s, 6H) . ESHRMS m/z 463.0782 (M+H C 22 H 22 BrF 2 N 2 0 2 requires 463.0827) Example 3-Bromo-4- (2,4-difluorobenzyloxy) - i- [3- ( isopropylaminomethyl ) benzyl ] - IHpyridin2 - one The title compound was prepared by a procedure similar the one described for Example 74 (0.06 g, 35%): mp 109-110 IH NMR (300 MHz, CDCI 3 ) 6 7.54 (d, J = 6 Hz, IH), 7.33-7.20 5H), 6.94-6.81 (m, 2H), 6.10 (d, J = 6 Hz, IH), 5.20 (s, 2H), 5.14 (s, 2H), 3.77 (s, 2H), 2.88 (t, J = 6 Hz, IH), 1.13 (d, = 6 Hz, 6H). ESHRMS m/z 477.0955 (M+H Cz 3 H 24 BrF 2 N 2 0 2 requires 477.0984) Example 76 F F O 3-Bromo-4- (2,4-difluorobenzyloxy) -i- [ (3dimethylaminomethyl ) benzyl ] - iH-pyridin-2 -one The title compound was prepared by a procedure similar the one described for Example 74 (0.06 g, 25%) : mp 103-107 H NMR (300 MHz, CDCI 3 ) 6 7.52 (d, J = 8 Hz, IH), 7.32-7.24 5H) , 6.94 (td, J = 9, 3 Hz, IH) , 6.84 (td, J = 9, 3 Hz, IH), 6.08 (d, J = 8 Hz, IH), 5.20 (s, 2H), 5.16 (s, 2H), 3.44 (s, 2H) , 2.24 (s, 6H). ESHRMS m/z 463.0801 (M+H C 22 H 22 BrFHN 2 0 2 requires 463.0827) . Example 77 0 H 3-Bromo-4-(2,4-difluorobenzyloxy)-l-[(3methylaminomethyl)benzyl]-iH-pyridin-2-one The title compound was prepared by a procedure similar the one described for Example 74 (0.05 g, 16%): mp 107-111 IH NMR (300 MHz, CDCI 3 ) 6 7.55 (d, J = 6 Hz, IH), 7.31-7.19 5H), 6.94-6.81 (m, 2H), 6.09 (d, J = 6 Hz, IH), 5.20 (s, 2H), 5.14 (s, 2H), 3.73 (s, 2H), 2.45 (s, IH). ESHRMS m/z 449.0652 (M+H C 21 H 20 BrF 2 N 2 0 2 requires 449.0671) Example 78 F BrO N NHBoc O {3-[3-Bromo-4-(2,4-difluorobenzyloxy)-2-oxo-2H-pyridin-lylmethyl]benzyl}carbamic acid tert-butyl ester The title compound was prepared essentially according to the procedure described in Example 70. mp 80-84 °C; IH NMR (300 MHz, DMSO-d 6 ) 6 7.60-7.50 (m, IH), 7.33-7.21 (m, 5H), 6.97-6.81 (m, 2H), 6.10 (dd, J = 8, 2 Hz, IH), 5.20 (s, 2H), 5.15 (s, 2H), 4.87 (br s, 2H), 4.30 (s, 2H) 1.45 (s, 9H) . ESHRMS m/z 535.1019 (M+H C 2 sH 2 BrF 2 N=O 4 requires 535. 1039) Example 79 l-[(3-Aminomethyl)benzyl]-3-bromo-4-(2,4-difluorobenzyloxy)- IH-pyridin-2-one Step I. Preparation of l-[(3-Aminomethyl)benzyl]-3-bromo-4- (2,4-difluorobenzyloxy)-IH-pyridin-2-one. To an ice-cold solution of {3- [3-Bromo-4-(2,4- difluorobenzyloxy)-2-oxo-2H-pyridin-l-ylmethyl]benzyl}carbamic acid tert-butyl ester (Example 78) (0.05 g, 0.I mmol) in CH 2 C1 2 (2 mL) was added TFA (2 mL), and the reaction mixture was stirred for 1 hour. The solvent was removed under reduced pressure to provide l-[(3-aminomethyl)benzyl]-3-bromo-4-(2,4- difluorobenzyloxy)-IH-pyridin-2-one as a tan solid (0.049 g, 100%), as the TFA salt: mp 80-84 °C; IH NMR (300 MHz, DMSO-d 6 ) 6 8.15 (br s, 3H), 7.97 (d, J = 8 Hz, IH), 7.79-7.60 (m, IH), 7.44-7.30 (m, 4H), 7.20-7.15 (m, IH), 6.61 (d, J = 6 Hz, IH), 5.31 (s, 2H), 5.16 (s, 2H), 4.03 (s, 2H); 19F NMR (282 MHz, DMSO- ) 6-74.56 (4.8F), -109.63 (IF), -113.61 (IF) . ESHRMS m/z 435.0540 (M+H C 20 HIsBrF 2 N 2 0 2 requires 435.0515) Example (isopropylaminomethyl)benzyl]-iH-pyridin-2-one Step i. Preparation of 3-Chloro-4-(2,4-difluorobenzyloxy)-lH- pyridin-2-one. To a solution of 4-[(4-fluorobenzyl)oxy]pyridine-2(iH)- one (from Step 2, Example 74) (1.4 g, 5.9 mmol] in AcOH (25 mL) was added N-chlorosuccinimide (0.95 g, 7.1 mmol) and the reaction mixture was heated at reflux for 2 h. The solvent was removed under reduced pressure. IH NMR (300 MHz, MeOD) 6 7.63-7.55 (m, IH), 7.45(d, J = 8 Hz, IH), 7.07-7.00 (m, 2H), 6.58 (d, J = 8 Hz, IH), 5.31 (d, J = 8 Hz, IH). Step 2. Preparation of 3-Chloro-l-(4-chloromethylbenzyl)-4- (2,4-difluorobenzyloxy)-iH-pyridin-2-one. 3-Chloro-l-(4-chloromethylbenzyl)-4-(2,4difluorobenzyloxy)-IH-pyridin-2-one was prepared by procedure similar to the one described for 3-bromo-l-(4-chloromethylbenzyl)-4-(2,4-difluorobenzyloxy)-iH-pyridin-2-one (Step 3, ) as white solid (0.24 g, 34%): IH NMR (300 MHz, CDCI 3 ) 6 7.53 (app q, J = 9 Hz, 1H), 7.34 (app q, J = 9 Hz, IH), 7.23 (d, J = 8 Hz, IH), 6.94 (td, J = i0, 2 Hz, IH), 6.85 (td, J = I0, 2 Hz, IH), 6.14 (d, J = 8 Hz, IH), 5.20 (s, 2H), 5.16 (s, 2H), 4.56 (s, 2H) . Step 3. Preparation of 3-Chloro-4- (2,4-difluorobenzyloxy)-l- [4 - ( isopropylamino-methyl ) benzyl ] - iH-pyridin2 -one. The title compound was prepared by a procedure similar to the one described for Example 74 (0.17 g, 69 %): mp 146-151 3.81 s, 2H), 2.98 (br s, IH), 1.20 (s, 6H). ESHRMS m/z 433.1481 (M+H C 2 Hz 4 CIF 2 N 2 0 2 requires 433.1489) Example 81 F\ S/ O 0 2 3-Chloro-4-(2,4-difluorobenzyloxy)-l-[(3methanesulfonyl)benzyl]-iH-pyridin-2-one Step i. Preparation of (3-Methanesulfonyl)phenyl methanol. To an ice-cold solution of 3-(methylsulfonyl)benzoic acid (1.4 g, 7.1 rnmol) in 2:1 Et 2 0/THF (60 mL) was added LiAIH 4 (8.5 mL of 1.0 M solution in THF, 8.5 mmol), and the reaction mixture was heated at reflux for 1 h. The reaction mixture was cooled to 0 °C, and the reaction was quenched with water (15 mL) and 15%NaOH in water (35 mL) . The reaction mixture was filtered, concentrated under reduced pressure, and the residue was dissolved in EtOAc. The organic solution was washed with water and then brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 1:2 to 3:1 EtOAc/hexanes) provided (3-methanesulfonyl)phenyl methanol as a clear oil (0.56 g, 42%): IH NMR (300 MHz, CDCI 3 ) 6 7.93 (s, IH), 7.83 (d, J = 7 Hz, IH), 7.64 (d, J = 7 Hz, IH), 7.53 (t, J = 7 Hz, IH), 4.78 (d, J = 6 Hz, 2H), 3.05 (s, 3H), 2.61 (br s, IH). Step 2. Preparation of l-Chloromethyl-3methanesulfonylbenzene. A solution of (3-methanesulfonyl)phenyl methanol (0.21 g, i.i mmol) in thionyl chloride (3 mL) was heated at 80 °C for 3 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure to provide lchloromethyl-3-methanesulfonylbenzene as a yellow oil (0.23 95%): " H NMR (300 MHz, CDCI 3 ) 6 7.98 (s, IH), 7.90 (d, J = 8 Hz, !H), 7.70 (d, J = 8 Hz, IH), 7.59 (t, J = 8 Hz, !H), 4.65 (s, 2H), 3.08 (s, 3H) . Step 3. Preparation of 3-Chloro-4-(2,4-difluorobenzyloxy)-l- [ (3-methanesulfonyl) -benzyl] - IH-pyridin-2-one. The title compound was prepared by a procedure similar to the one described for Example 80 (0.14 g, 78%): mp 155-157 °C; H NMR (300 MHz, CDCI 3 ) 6 7.88 (d, J = 8 Hz, IH), 7.83 (m, IH), 7.67 (d, J = 8 Hz, IH), 7.58-7.48 (m, 2H), 7.31 (d, J = 8 Hz, IH), 6.95-6.83 (m, 2H), 6.22 (d, J = 8 Hz, IH), 5.22 (s, 4H), 3.08 (s, 3H) . ESHRMS m/z 440.0525 (M+H C 20 HIvCIF 2 NO 4 S requires 440.0529) Example 82 0 2 CI N 3-Chloro-4- (2,4-difluorobenzyloxy) -I- [ (4methanesulfonyl)benzyl]-IH-pyridin-2-one The title compound was prepared by a procedure similar to the one described for Example 81 (0.08 g, 73% : rap 223-225 °C; IH NMR (300 MHz, CDCI 3 ) 6 7.91 (d, J = 8 Hz, 2H), 7.53-7.47 (m, 3H), 7.30-7.26 (m, IH), 6.94-6.86 (m, 2H) 6.22 (d, J = 8 Hz, IH), 5.23 (s, 4H), 3.03 (s, 3H) . ESHRMS m/z 440.0512 (M+H C 20 HI CIF 2 NO 4 S requires 440. 0529) ylmethyl]benzamide Step i. Preparation of Methyl 4- [3-chloro-4-(2,4di f luorobenzyloxy) - 2oxo2 Hpyr idin1 - ylmethyl ] benzoate. Methyl 4- [3-Chloro-4- (2,4-difluorobenzyloxy)-2-oxo-2H-pyridinl-ylmethyl]benzoate was prepared by a procedure similar to the one described for Example 81 (0.14 g, 60%): IH NMR (300 MHz, CDCI 3 ) 6 8.01 (dd, J = 8, 2 Hz, IH), 7.52 (app q, J = 8 Hz, IH) , 7.36 (d, J = 9 Hz, 2H), 7.26-7.22 (m, 2H) , 6.94 (td, J = 8, 2 Hz, IH), 6.85 (td, J = 8, 2 Hz, IH), 6.16 (d, J = 9 Hz, IH), 5.21 (s, 4H), 3.92 (s, 3H) . Step 2. Preparation of 4-[3-Chloro-4-(2,4-difluorobenzyloxy)- 2-oxo-2H-pyridin-l-ylmethyl]benzamide. A sealed tube containing a solution of 4-[3-Chloro-4-(2,4difluorobenzyloxy)-2-oxo-2H-pyridin-l-ylmethyl]benzoic acid methyl ester (0.25 g, 0.60 mmol) and N-H 3 (20 mL of a 7 N solution in MeOH, 140 mmol) was heated at 75 °C for 16 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. Trituration with Et 2 0/MeOH afforded 4-[3-Chloro-4-(2,4-difluorobenzyloxy)-2-oxo2H-pyridin-l-ylmethyl]benzamide as a white solid (0.14 g, Example 84 F30yoH 0 C! 3-Chloro-4-(2,4-difluorobenzyloxy)-l-isoquinolin-5-ylmethyliH-pyridin~2-one Step 1. Preparation of Isoquinolin-5-y!methanol. To an ice-cold solution of isoquinoline-5-carbaldehyde (0.68 g, 4.3 mmol) in MeOH (15 mL) was added NaBH 4 (0.17 g, 4.6 mmol), and the reaction mixture was stirred for 15 min. The reaction was quenched with brine, the solvent was removed under reduced pressure, and the residue was dissolved in EtOAc. The organic solution was washed with water and then brine, dried (Na 2 SO 4 ), filtered, and concentrated under reduced pressure to afford isoquinolin-5-ylmethanol as a brown solid (0.63 g, 93%) : IH N-MR (300 MHz, DMSO- ) 6 9.87(s, IH), 8.82 (d, J = 6 Hz, IH), 8.57 (d, J= 6 Hz, IH), 8.47 (d, J = 9 Hz, IH), 8.30 (d, J = 6 Hz, IH), 7.95 (t, J = 9 Hz, IH), 5.34 (s, 2H) . Step 2. Preparation of 5-Bromomethylisoquinoline. To a solution of isoquinolin-5-ylmethanol (0.63 g, 3.9 mmol) in AcOH (3.3 mL) was added HBr (6.6 mL, a 30% w/w solution in AcOH, 24 mmol), and the reaction mixture was stirred at 75 °C for 45 min. The reaction mixture was cooled to room temperature, and the precipitate was collected to provide the 5-bromomethylisoquinoline hydrobromide acid salt as a brown solid (i.i g, 87%): IH NMR (300 MHz, CDCI 3 ) 6 9.22 (s, IH}, 8.58 (d, J = 6 Hz, IH), 7.95-7.89 (m, 2H) , 7.76 (d, J =9 Hz, IH), 7.59 (dd, J = 9, 6 Hz, IH) , 5.16 (s, 2H) . Step 3. Preparation of 3-Chloro-4-(2,4-difluorobenzyloxy)-lisoquinol in5 - ylmethyl - iH-pyridin2 -one. The title compound was prepared by a procedure similar to the one described for Example 81, as the TFA salt (0.13 g, 33%): mp 235-238 °C; H NMR (300 MHz, DMSO-d 6 ) 6 9.55 (s, IH), 8.66 (d, J = 6 Hz, IH), 8.29 (d, J = 6 Hz, IH), 8.22 (d, J = 8 Hz, IH), 7.91 (d, J = 8 Hz, IH), 7.77 (t, J = 8 Hz, IH), 7.65-7.63 (m, IH), 7.53 (d, J = 7 Hz, IH), 7.35-7.25 (m, IH), 7.20-7.10 (m, IH), 6.68 (d, J = 8 Hz, IH), 5.67 (s, 2H), 5.32 (s, 2H) ; I F NMR (282 MHz, DMSO-d 6 ) 6 -74.79 (3F) , -109.43 (IF) , -113.62 (IF) . ESHRMS m/z 413.0868 (M+H C 22 HI 6 CIF 2 N 2 0 3 requires 413.0863) Example F O 3-Chloro-4-(2,4-difluorobenzyloxy)-l-(l,2,3,4tetrahydroisoquinolin-5-ylmethyl)-iH-pyridin-2-one Step I. Preparation of 3-Chloro-4-(2,4-difluorobenzyloxy)-l- (l,2,3,4-tetrahydro-isoquinolin-5-ylmethyl)-IH-pyridin-2-one. To a solution of 3-chloro-4-(2,4-difluorobenzyloxy)-lisoquinolin-5-ylmethyl-iH-pyridin-2-one (Example 84) (0.14 g, 0.34 mmol) in AcOH (1.3 mL) was added NaCNBH (0.09 g, 1.4 mmol), and the reaction mixture was stirred for 2 h. The reaction mixture was cooled to 0 °C, and diluted with water(10 mL) and 40% aqueous NaOH (I0 mL), and the aqueous layer was washed with EtOAc (3 x 50 mL). The combined organics were washed with brine, dried (Na 2 S0 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 98:1.8:0.2 to 88:10.8:1.2 CH 2 CI 2/MeOH/NH 3) provided 3-chloro-4- (2,4-difluoro-benzyloxy)- i- (i, 2,3,4-tetrahydroisoquinolin-5-ylmethyl) -iH-pyridin-2-one as a white solid (0.13 g, 92%): mp 180-184 °C; IH NMR (300 MHz, MeOD) 6 7.65-7.55 (m, 2H) , 7.16-7.00 (m, 4H) , 6.90-6.80 (m, IH), 6.60 (d, J = 8 Hz, IH), 5.31 (s, 2H), 5.20 (s, 2H), 4.06 (s, 2H), 3.21 (t, J = 6 Hz, 2H), 2.82 (t, J = 6 Hz, 2H). ESHRMS m/z 417.1173 (M+H C 22 H 20 CIF 2 N 2 0 2 requires 417.1176) Example 86 Cl 3-Chloro-4- (2,4-difluorobenzyloxy) -i- (iH-indol-5-ylmethyl) - IHpyridin2 - one Step i. Preparation of 5-(Carboxymethyl)-indole-l-carbamic acid tert-butyl ester. To a solution of methyl indole-5-carboxylate (6.9 g, 39 mmol) and Et 3 N (6.0 mL, 43 mmol) in CH 2 C1 2 (150 mL) was added ditert-butyl dicarbonate (19 g, 86 mmol), and the reaction mixture was stirred for 14 h. The reaction mixture was diluted with CH 2 C1 2 , washed with water and then brine, dried (Na 2 SO 4), filtered, and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, 3:7 EtOAc/hexanes) provided 5-(carboxymethyl)-indolel-carbamic acid tert-butyl ester as a light yellow oil (ii g, 100%) : IH NMR (300 MHz, CDCI 3 ) 6 8.29 (s, IH), 8.15 (d, J = 9 Hz, IH), 7.93 (d, J = 9 Hz, IH), 7.78 (d, J = 3 Hz, IH), 6.85 (d, J = 3 Hz, IH), 3.91 (s, 3H), 1.68 (s, 9H) . Step 2. Preparation of 5-Hydroxymethylindole-l-carbamic acid tert-butyl ester. To a -78 °C solution of 5-(carboxymethyl)-indole-l-carbamic acid tert-butyl ester (10.8 g, 39 mmol) in THF (180 mL) was added DIBAL (127 mL of a 1 M solution in THF, 127 mmol), and the reaction mixture was stirred for 2.5 h. The reaction was quenched with I:I I N HCI/MeOH (i00 mL), the reaction mixture was warmed to room temperature, diluted with CHIC1= (i00 mL), and separated. The organic solution was washed with saturated Rochelle salt, dried (Na 2 S0 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, i:i EtOAc/hexanes) provided 5-hydroxymethylindole-lcarbamic acid tert-butyl ester as a yellow oil (6.5 g, 68%): IH NMR (300 MHz, CDCI 3 ) 6 8.07 (d, J = 9 Hz, IH), 7.59 (d, J = 6 Hz, IH), 7.54 (s, IH), 7.28 (d, J = 9 Hz, IH), 6.58 (d, J = 6 Hz, IH) , 4.73 (s, 2H), 1.97 (s, 9H) . Step 3. Preparation of 5-Bromomethylindole-l-carbamic acid tert-butyl ester. To an ice-cold solution of 5-hydroxymethylindole-l-carbamic acid tert-butyl ester (0.51 g, 2.1 mmol) in 4:1 Et 2 0/CH 2 CI 2 (4 mL) was added PBr 3 (0.2 mL, 2.2 mmol), and the reaction mixture was stirred for 40 min. The reaction mixture was diluted with CH 2 C1 2, washed a saturated solution of NaHC0 3 (3 x i0 mL), dried (Na 2 SO 4 ), filtered, and the solvent was removed under reduced pressure to provide 5-bromomethyl~indole-l-carbamic acid tert-butyl ester as a yellow solid (0.59 g, 93%). !H NMR Step 4. Preparation of 5- [3-Chloro-4- (2,4-difluorobenzyloxy) 2-oxo-2H-pyridin-l-ylmethyl]indole-l-carbamic acid tert-butyl ester. 5- [3-Chloro-4- (2,4-difluorobenzyloxy) -2-oxo-2H-pyridin-lylmethyl]indole-l-carbamic acid tert-butyl ester was prepared by a procedure similar to the one described for Example 81 as an off-white solid (0.54 g, 67%): H NMR (300 MHz, CDCI 3 ) 6 8.10 (d, J = 8 Hz, IH), 7.60 (d, J = 3 Hz, 2H), 7.52 (m, IH), 7.26 (m, IH), 6.94 (td, J = 9, 2 Hz, IH), 6.84 (td, J = 9, 2 Hz, IH) 6.53 (d, J = 2 Hz, IH), 6.08 (d, J = 8 Hz, IH), 5.25 (s, 2H), 5.18 (s, 2H), 1.66 (s, 9H). Step 5. Preparation of 3-Chloro-4- (2,4-difluorobenzyloxy)-l- ( IHindol - 5 -ylmethyl ) - IHpyridin2 - one. A flask containing 5- [3-chloro-4- (2,4-difluorobenzyloxy)-2oxo-2H-pyridin-l-ylmethyl]indole-l-carbamic acid tert-butyl ester (0.48 g, 0.96 mmol) was heated at 150 °C for 4 h. The reaction mixture was cooled to room temperature, and purification by preparatory HPLC (Phenomenex Luna C18(2) column, 250 x 21.20 ram, I0 Solvent A: 0.05% TFA in 95:5 H 2 0/CHHCN; Solvent B: 0.05% TFA in 95 : 5 CHHCN/H 2 0 Eluent: 30-95% B over 20 min; flow 20.0 mL/min; UV Detector: 254 nm; Retention Time: 15.6 rain) provided 3-chloro-4- (2, 4difluorobenzyloxy) -I- (IH-indol-5-ylmethyl) -IH-pyridin-2-one as an off-white solid (0.14 g, 36%): mp 152-153 °C; IH NMR (300 ESHRMS m/z 401.0845 (M+H CnHI 6 CIF=N 2 0 2 requires 401.0863). Example 87 c 1/ N-./x-J l-(l~Acetyl-iH-indol-5-ylmethyl)-3-chloro-4-(2,4difluorobenzyloxy)-iH-pyridin-2-one To a solution of 3-chloro-4- (2,4-difluorobenzyloxy)-l-(iHindol-5-ylmethyl)-iH-pyridin-2-one (Step 5, synthesis of Example 86 ) (0.22 g, 0.57 mmol) in CH 3 CN (I0 mL) was added acetic anhydride (0.06 mL, 0.58 mmol) and Et N (2 mL) , and the reaction mixture was stirred at 86 °C for 6 h. The reaction mixture was cooled to room temperature, and partitioned between 1 N HCI and EtOAc. The organic solution was separated, washed with brine, dried (Na 2 SO 4 ), filtered, and concentrated under reduced pressure. IH NMR (300 MHz, MeOD) 8.35 (d, J = 9 Hz, IH), 7.77 (d, J = 9 Hz, IH), 7.70 (d, J = Hz, IH), 7.54 (s, 2H), 7.31 (d, J = 9 Hz, IH), 7.01-6.99 (m, 2H), 6.66 (d, J = 3 Hz, IH), 6.59 (d, J = 9 Hz, IH), 5.29 (s, 4H), 2.63 (s, 3H). ESHRMS m/z 443.0965 (M+H C 23 HIsCIF 2 N 2 0 requires 443.0969). Example 88 ylmethyl)-IH-pyridin-2-one To a solution of 3-chloro-4-(2,4-difluorobenzyloxy)-l-(iHindol-5-ylmethyl)-IH-pyridin-2-one (Step 5, synthesis of Example 86 ) (0.24 g, 0.60 mmol) in AcOH (5 mL) was added NaCNBH 3 (0.06 g, 1.0 mmol), and the reaction mixture was stirred for 1 h. The reaction mixture was partitioned between water and EtOAc, and the precipitate was collected by filtration. Trituration with CH 2 C1 2 afforded 3-Chloro-4-(2,4difluorobenzyl-oxy)-l-(2,3-dihydro-iH-indol-5-ylmethyl)-iHpyridin-2-one as a white solid (0.2 g, 81%): mp 137-139 °C; IH NMR (300 MHz, CDCIa) 6 7.51 (app q, J = 9 Hz, IH), 7.21 (d, J = 6 Hz, IH), 7.11 (s, IH), 6.99-6.80 (m, 3H), 6.57 (d, J = 9 Hz, IH), 6.08 (d, J = 9 Hz, IH), 5.18 (s, 2H), 5.02 (s, 2H), 3.83 (br s, IH), 3.55 (t, J = 9 Hz, 2H), 2.99 (t, J = 9 Hz, 2H). ESHRMS m/z 403.1022 (M+H CnHIsCIF 2 N 2 0 2 requires 403.1019). The following example compounds were prepared by procedures similar to that described for Example 74. The yields and the analytical data of the title compounds are reported below. Examples 89-101. The compounds of Examples 89-101 are prepared essentially according to the procedures set forth above for Example 74. The yield (Y), molecular formula (MF) and analytical data for these compounds are shown below. Example No. R Ex. 89 pyridine-3-ylmethyl Ex. 90 pyridin-4-ylmethyl Ex. 91 pyridin-2-ylmethyl Ex. 92 4-tert-butyl)benzyl Ex. 93 3-methoxybenzyl Ex. 94 Benzo[l,3]dioxol-5ylmethyl Ex. 95 2-fluorobenzyl Y M+H ESHRMS MF Requires m/z C 18 HI 3 BrF 2 N 2 0 2 407.0202 407.0197 ICI HI BrF 2 N 2 0 2 407.0202 407.0189 56 C 18 HI BrF 2 N 2 0 2 407.0201 407.0184 32 C 23 H 22 BrF 2 NO 2 462.0875 462.0863 IC 20 HI 6 BrF 2 NO 436.0354 436.0353 450.0147 450.0136 424.0155 424.0143 %) : mp 179-182 °C; IH NMR (300 MHz, CDCI 3 ) 7.58-7.53 (m, 3H) , 7.33-7.26 (m, IH) , 7.14-7.02 (m, 2H) , 6.96-6.82 (m, 2H) , 6.11 (d, J = 9 Hz, IH), 5.20 (s, 2H), 5.18 (s, 2H) . ESHRMS m/z (M+H requires) . Example 96 3-Bromo-4- (2,4-difluorobenzyloxy) -i- (2,4-difluorobenzyl) -IHpyridin2 - one Step I. Preparation of 4-(2,4-Difluorobenzyloxy)-l-(2,4di f I uorobenzyl ) - 1 H-pyridin - 2 - one. To a solution of 2,4-dihydroxypyridine (0.35 g, 3.2 mmol) in DMF (50 mL) was added K 2 C0 3 (2.5 g, 13 mmol) and 9-,4difluorobenzyl bromide (I.0 mL, 7.6 mmol), and the reaction mixture was stirred at Ii0 °C for 4 h. The reaction mixture was cooled to room temperature, diluted with brine, and extracted with CHCI 3 (4 x i00 mL). The combined organics were washed with water and then brine, dried (Na 2 SO 4 ), filtered, and concentrated under reduced pressure. IH NMR (300 MHz, CDCI 3 ) 7.54 (app q, J = 8 Hz, IH) , 7.38-7.28 (m, 5H) , 6.94 (td, J = 8, 2 Hz, IH), 6.85 (td, J = 8, 2 Hz, IH), 6.10 (d, J = 9 Hz, IH), 5.21 (s, 2H), 5.16 (s, 2H), 4.56 (s, 2H) . Step 2. Preparation of 3-Bromo-4-(2,4-difluorobenzyloxy)-l- (2,4-fluorobenzyl)-iH-pyridin-2-one. To an ice-cold solution of 4-(2,4-difluorobenzyloxy)-l-(2,4difluorobenzyl)-iH-pyridin-2-one (0.72 g, 2.0 mmol) in AcOH (4.0 mL) was added a solution of bromine (0.II mL, 2.2 mmol) in AcOH (7.2 mL), and the reaction mixture was stirred for min. The solvent was removed under reduced pressure. IH NMR (300 MHz, CDCI 3 ) 6 7.63-7.45 (m, 2H), 7.42 (d, J = 6 Hz, IH), 6.93-6.77 (m, 4H), 6.12 (d, J = 6 Hz, iH), 5.20 (s, 2H), 5.12 (s, 2H). ERMS m/z M+H 442. Example 97 O {3- [3-Bromo-4- (2,4-difluorobenzyloxy) -2-oxo-2H-pyridin-lylmethyl] -phenyl } acetonitrile Step i. Preparation of Methyl 3-cyanomethylbenzoate. To an ice-cold solution of methyl 3-bromomethylbenzoate (9.1 g, 40 mmol) in CH 3 CN (108 mL) was added tetrabutylammonium fluoride (17.3 mL, 60 mmol) and trimethylsilylcyanide (8.0 mL, mmol), and the reaction mixture was heated at reflux for h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, I:i EtOAc/hexanes) provided methyl 3-cyanomethylbenzoate as a clear oil (3.0 g, 43%): H NMR (300 MHz, DMSO-d ) 6 7.97 (s, IH), 7.92 (d, J = 8 Hz, IH), 7.64 (d, J = 8 Hz, IH), 7.56 (t, J = 8 Hz, IH), 4.16 (s, 2H), 3.87 (s, 3H) . Step 2. Preparation of (3-Hydroxymethylphenyl)acetonitrile. To an ice-cold solution of methyl 3-cyanomethylbenzoate (2.8 g, 18 mmol) in THF (23 mL) was added LiBH 4 (8.8 mL of a 2 M solution in THF, 18 mmol), and the reaction mixture was heated at reflux for 4 h. The reaction mixture was cooled to room temperature, the reaction was quenched with i:i water/l N HCI, and the aqueous layer was washed with EtOAc (3 x 150 mL). The combined organics were washed with brine, dried (MgS0 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 2:1 EtOAc/hexanes) provided (3-hydroxymethylphenyl)-acetonitrile as a clear oil (0.97 g, 41%): IH NMR (300 MHz, MeOD) 6 8.158.08 (m, IH), 7.47-7.34 (m, IH), 7.27 (s, IH), 6.97-6.82 (m, IH), 4.87 (s, 2H), 3.91 (s, 2H) Step 3. Preparation of (3-Bromomethylphenyl)acetonitrile. To an ice-cold solution of (3-hydroxymethylphenyl)acetonitrile (0.97 g, 7.3 mmol) in THF (35 mL) was added CBr 4 (2.5 g, 7.7 mmol) and Ph 3 P (2.0 g, 7.7 mmol), and the reaction mixture was stirred for 3 h. The reaction mixture was filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 1:9 to 1:4 EtOAc/hexanes) provided (3-bromomethylphenyl)acetonitrile as a clear oil (0.89 g, 58%): IH NMR (300 MHz, MeOD) 6 7.47-7.29 (m, IH), 7.27 (s, IH), 6.97-6.82 (m, IH), 4.87 (s, 2H), 3.91 (s, 2H) . Step 4. Preparation of {3- [3-Bromo-4-(2,4-difluorobenzyloxy)- 2 -oxo2H-pyridinl-ylmethyl ] phenyl } acetonitrile. The title compound was prepared by a procedure similar to the one described for Example 74 (0.07 g, 10%): mp 120-121 °C; IH NMR (300 MHz, CDCI 3 ) 6 7.60-7.50 (m, IH), 7.37-7.27 (m, 5H), 6.96 (td, J = 9, 3 Hz, IH), 6.82 (td, J = 9, 3 Hz, IH), 6.13 (d, J = 8 Hz, IH), 5.21 (s, 2H), 5.16 (s, 2H). ESHRMS m/z 445.0381 (M+H C 21 HI BrF 2 N 2 0 2 requires 445.0358). Example 98 ylmethyl]benzonitrile The title compound was prepared by a procedure similar to the one described for Example 74 (0.13 g, 47%) : mp 194-197 °C; IH NMR (300 MHz, CDCI 3 ) 6 7.75 (d, J = 9 Hz, IH), 7.69-7.49 (m, 4H) , 7.42 (t, J = 8 Hz, IH) , 6.96-6.73 (m, 2H), 6.18 (d, J = 8 Hz, H), 6.17 (s, 2H), 5.30 (s, 2H) . ESHRMS m/z 431.0210 (M+H C 20 H 4 BrF 2 N 2 0 2 requires 431.0201. Example 99 F Br 0 NH 2 i- [ (2-Aminomethyl) benzyl) ] -3-bromo-4- (2,4-difluorobenzyloxy) - iH-pyridin2- one To a solution of 2-[3-bromo-4-(2,4-difluorobenzyloxy)-2-oxo2H-pyridin-l-ylmethyl]-benzonitrile (0.ii g, 0.25 mmol) in THF (3 mL) was added BH -DMS (0.25 mL of a 2.0 M solution in THF, 0.5 mmol), and the reaction mixture was stirred at 70 °C for 1 h. The reaction mixture was cooled to 0 °C, and the reaction :4a che wi h MeQ The solvent was removed under reduced pressure, and the residue was partitioned between 2N NaOH and EtOAc. The organic solution was washed with brine, dried (MgSO 4), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 90:9:1 methylene chloride/methanol/ammonia) provided l-[(2-aminomethyl)benzyl]- 3-bromo-4- (2,4-difluorobenzyloxy)-iH-pyridin-2-one as a white solid (0.15 g, 48%): IH NMR (300 MHz, CDCI 3 ) 6 7.55 (app q, J = 8 Hz, IH) , 7.40-7.26 (m, 4H), 7.14 (d, J = 8 Hz, IH), 6.94 (td, J = 8, 2 Hz, IH), 6.85 (td, J = 8, 2 Hz, IH), 6.08 (d, J = 8 Hz, IH) , 5.31 (s, 2H) , 5.21 (s, 2H) 4.03 (s, 2H) . ESHRMS m/z 435.0517 (M+H C 20 HIsBrF 2 N 2 0 2 requires 435.0514). Example !00 F O 0 0 Methyl 3- [3-Bromo-4- (2,4-difluorobenzyloxy)-2-oxo-2H-pyridinl-ylmethyl ] benzoate The title compound was prepared by a procedure similar to the one described for Example 74 (0.05 g, 11%): mp 115-117 °C; IH NMR (300 MI4z, CDCI 3 ) 6 8.15-7.95 (m, 2H), 7.65-7.50 (m, 2H), 7.45-7.40 (m, IH), 7.32 (d, J = 6 Hz, IH), 7.00-6.80 (m, 2H), 6.12 (d, J = 9 Hz, IH), 5.21 (s, 2H), 5.20 (s, 2H), 3.92 (s, 3H).. ESHRMS m/z 464.0292 (M+H CnHITBrF 2 NO 4 requires 464.0303). Example i01 Methyl 4- [3-Bromo-4- (2,4-difluorobenzyloxy) -2-oxo-2H-pyridin1 -ylmethyl ] -benzoate The title compound was prepared by a procedure similar to the one described for Example 74 (0.17 g, 46%): mp136-139 °C; IH NMR (300 MHz, CDCI 3 ) 6 8.01 (d, J = 8 Hz, 2H), 7.60-7.51 (m, IH), 7.37 (d, J = 8 Hz, 2H), 7.29-7.26 (m, IH), 6.93 (td, J = 9, 2 Hz, IH), 6.84 (td, J = 9, 2 Hz, 1H), 6.13 (d, J = 8 Hz, IH), 5.23 (s, 4H), 3.91 (s, 3H) . ESHRMS m/z 464.0306 (M+H C 21 HIvBrF 2 NO 2 requires 464.0304). Example 102 0 0 3-[3-Bromo-4-(2,4-difluorobenzyloxy)-2-oxo-2H-pyridin-lylmethyl]benzamide A sealed tube containing a solution of methyl 3-[3-bromo-4- (2,4-difluorobenzyloxy)-2-oxo-2H-pyridin-l-ylmethyl]benzoate (0.i g, 0.21 mmol) and NH 3 (3 mL of a 7 N solution in MeOH, 21 mmol) was heated at 75 °C for 16 h. The reaction mixture was cooled to room temperature and the solvent was_ emoved under reduced pressure. Trituration with Et 2 0/MeOH:ia brd d< a wh±t 5.32 (s, 2H), 5.18 (s, 2H) . ESHRMS m/z 449.0295 (M+H C 20 HI BrF 2 N 2 0 3 requires 449.0307). Example 103 O 4- [3-Bromo-4- (2,4 -difluorobenzyloxy) -2-oxo-2H-pyridin-1ylmethyl ] benzamide The title compound was prepared by a procedure similar to the one described for Example 102 from Example I01 (0.04 g, 12%): mp 235-238 °C; IH NMR (300 MHz, DMSO-d ) 6 8.00 (d, J Hz, IH), 7.94 (br s, IH), 7.78 (d, J = 8 Hz, IH), 7.64 (app J = 8 Hz, IH), 7.38-7.30(m, 4H), 7.17 (td, J = 6, 2 Hz, IH), 6.60 (d, J = 9 Hz, IH) , 5.27 (s, 2H) , 5.14 (s, 2H) . ESHRMS m/z 449.0291 (M+H C 20 HI 6 BrF 2 N O 3 requires 449.0307). Example 104 O F I- (3-Aminomethyl-2fluorobenzyl) - 3-bromo-4- (2,4di f luorobenzyloxy) - iH-pyridin2 -one Step i. Preparation of 3-Bromo-l-(3-bromomethyl-2fluorobenzyl)-4-(2,4-difluoro-benzyloxy)-IH-pyridin-2-one. To a solution of 3-bromo-4-(2,4-difluorobenzyloxy)-iH-pyridin2-one (from Step 3, Example 74) (0.3 g, 0.95 mmol) in DMF (26 mL) was added K 2 CO (0.26 g, 1.9 mmol) and 2,6bis(bromomethyl)fluorobenzene (1.6 g, 5.7 mmol), and the reaction mixture was stirred at ii0 °C for 3 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was diluted with a 50% aqueous solution of brine, and the aqueous layer was extracted with EtOAc (3 x 50 mL). The combined organics were washed with water, dried (Na 2 SO 4 ), filtered, and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, eluent 99:1 to 95:5 methylene chloride/methano!) afforded 3-bromo-l-(3-bromomethyl-2fluorobenzyl)-4-(2,4-difluorobenzyloxy)-IH-pyridin-2-one as an off-white solid (0.24 g, 49%): IH NMR (300 MHz, CDCI 3 ) 6 7.557.40 (m, 3H), 7.35-7.25 (m, IH), 7.10-7.05 (m, IH), 7.00-6.80 (m, 2H), 6.14 (d, J = 6 Hz, IH), 5.22 (s, 2H), 5.19 (s, 2H), 4.50 (s, 2H) . Step 2. Preparation of l-(3-Aminomethyl-2-fluorobenzyl)-3bromo-4-(2,4-difluoro-benzyloxy)-IH-pyridin-2-one. A sealed tube containing a solution of 3-bromo-l-(3bromomethyl-2-fluorobenzyl)-4-(2,4-difluorobenzyloxy)-iHpyridin-2-one (0.24 g, 0.45 mmol) and NH 3 (24 mL of a 7 N solution in MeOH, 168 mmol) was heated at 80 °C for 1 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, eluent 99.5:0.5 to 96:4 methylene chloride/methanol) afforded a white solid (0.12 g, (s, 2H), 3.90 (s, 2H). ESHRMS m/z 453.0442 (M÷H C 20 HI BrFHN 2 0 2 requires 453.0420). Example 105 0 F 0 Methyl 3- [3-chloro-4- (2,4-difluorobenzyloxy)-2-oxo-2H-pyridin1 -ylme thyl ] - 2 - f luoro-benzoate Step i. Preparation of Methyl 2-fluoro-3-methylbenzoate. To a solution of 2-fluoro-3-methyl benzoic acid (3.57 g, 23 mmol) in MeOH (40 mL) was added concentrated sulfuric acid (2.3 mL), and the reaction mixture was heated at reflux for 12 h. The reaction mixture was cooled, the solvent was removed under reduced pressure, and the residue was dissolved in EtOAc. The organic solution was washed with a saturated solution of NaHCO 3 and then brine, dried (Na 2 SO 4 ), filtered and concentrated under reduced pressure to afford methyl 2-fluoro3-methylbenzoate as a yellow oil (3.2 g, 82%): IH NMR (300 MHz, CDCI 3) 6 7.76-7.71 (m, IH), 7.39-7.34 (m, IH), 7.08 (t, J = 8 Hz, IH), 3.98 (s, 3H) , 2.31 (d, J = 3 Hz, 3H) . Step 2. Preparation of Methyl 3-bromomethyl-2-fluorobenzoate. To a mixture of methyl 2-fluoro-3-methylbenzoate (1.5 g, 8.9 mmol) and N-bromosuccinimide (1.67 g, 9.4 mmol) was added carbon tetrachloride (24 mL) and benzoyl peroxide (5 mg), and the mixture was heated at reflux for 16 h. The reaction mixture was cooled, filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 5:95 to 60:40 EtOAc/hexanes) afforded methyl 3-bromomethyl-2-fluorobenzoate as a light yellow solid (0.91 g, 41% ) : IH NMR (300 MHz, CDCI 3 ) 6 7.93-7.88 (m, IH), 7.617.56 (m, IH), 7.20 (t, J = 8 Hz, IH), 4.53 (d, J = 3 Hz, 2H), 3.94 (s, 3H) . Step 3. Preparation of Methyl 3-[3-chloro-4-(2,4di f luorobenzyloxy) - 2 - oxo - 2 Hpyridin1 - ylmet hyl ] - 2 - fluorobenzoate. Methyl 3- [3-chloro-4-(2,4-difluorobenzyloxy)-2-oxo-2H-pyridinl-ylmethyl]-2-fluorobenzoate was prepared by a procedure similar to the one described for Example 81 (0.33 g, 69%): mp 171-174 °C; IH NMR (300 MHz, CDCI 3 ) 6 7.89-7.84 (m, 2H) , 7.607.45 (m, 2H), 7.25-7.15 (m, IH), 7.00-6.80 (m, 2H), 6.17 (d, = 6.0 Hz, IH), 5.21 (s, 2H), 5.19 (s, 2H), 3.93 (s, 3H) . ESHRMS m/z 438.0747 (M+H C 21 HIGCIF 3 NO 4 requires 438.0714). Example 106 F o F O 3- [3-Chloro-4- (2,4-difluorobenzyloxy) -2-oxo-2H-pyridinl- ylmeth¥1 ] - 2 - f luoro-benzamide The title compound was prepared by a procedure similar to the one described for Example 99 (0.15 g, 62%) : mp 252-254 °C; 6.80 (d, J = 8 Hz, IH), 5.46 (s, 2H), 5.33 (s, 2H). ESHRMS m/z 423.0710 (M+H C= 0 HIsCIFHN 2 0 3 requires 423.0718). Example 107 F F 3-Bromo-4-(2,4-difluorobenzyloxy)-l-(3-fluorobenzyl)-iHpyridin-2-one Step i. Preparation of 4-Benzyloxy-l-(3-fluorobenzyl)-iHpyridin-2-one. To a solution of 4-benzyloxy-IH-pyridin-2-one (I.0 g, 5 mmol) and K 2 CO 3 (2.0 g, 9.9 mmol) in DMF (30 mL) was added 3fluorobenzyl bromide (1.4 g, 7.5 mmol), and the reaction mixture was heated to ii0 °C for 3 h. The reaction mixture was cooled to room temperature, and partitioned between EtOAc and water. The organic solution was washed with water and then brine, dried (Na SO 4 ), filtered and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 97:3 to 93:7 methylene chloride /methanol) afforded 4-benzyloxy-l-(3-fluorobenzyl)-IH-pyridin-2-one (1.04 g, 67% ) : IH NMR (300 MHz, CDCI ) 6 7.45-7.25 (m, 5H), 7.13 (d, J = 8 Hz, IH), 7.10-6.90 (m, 3H), 6.10-5.95 (m, 2H), 5.07 (s, 2H) , 5.00 (s, 2H) . Step 2. Preparation of l-(3-Fluorobenzyl)-4-hydroxy-iHTo a solution of 4-benzyloxy-l-(3-fluorobenzyl)-iH-pyridin-2one (1.79 g, 5.8 mmol) in EtOH (50 mL) was added 10% Pd/C (0.4 g), and reaction mixture was stirred under a hydrogen atmosphere for 1.5 h. The reaction mixture was filtered through diatomaceous earth and concentrated under reduced pressure to give l-(3-fluorobenzyl)-4-hydroxy-iH-pyridin-2-one (0.92 g, 72% ) : IH NMR (300 MHz, CDCI 3 ) 6 7.55 (d, J = 6 Hz, IH) , 7.40-7.30 (m, IH) , 7.10-6.95 (m, 3H) , 6.07 (dd, J = 6, 3 Hz, IH), 5.85 (d, J = 3 Hz, IH), 5.11 (s, 2H) . Step 3. Preparation of 3-Bromo-l-(3-fluorobenzyl)~4-hydroxyIH-pyridin-2-one. To an ice-cold solution of l-(3-fluorobenzyl)-4-hydroxy-iHpyridin-2-one (0.67 g, 3.1 mmol) in AcOH (5.7 mL) was added a solution of bromine (0.52 g, 3.24 mmol) in AcOH (10.8 mL), and the reaction mixture was stirred for 5 min. The reaction mixture was warmed to room temperature and concentrated under reduced pressure to afford 3-bromo-l-(3-fluorobenzyl)-4hydroxy-iH-pyridin-2-one as a yellow solid (1.07 g, crude): iH NMR (500 MHz, MeOD) 6 7.64 (d, J = 8 Hz, IH), 7.35-7.30 (m, IH), 7.05-6.90 (m, 3H) , 6.20 (d, J = 8 Hz, IH), 5.18 (s, 2H) . Step 4. Preparation of 3-Bromo-4-(2,4-difluorobenzyloxy)-l- ( 3 - f luorobenzyl ) - iH-pyridin2 -one. To a solution of 3-bromo-l-(3-fluorobenzyl)-4-hydroxy-iHpyridin-2-one (0.20 g, 0.67) and K 2 C0 3 (0.27 g, 1.34 mmol) in acetone (i0 mL) was added 2,4-difluorobenzyl bromide (0.16 g, 0.8 mmol), and the reaction mixture was heated at reflux for 1 h. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and the residue was dissolved in EtOAc. The organic solution was washed with water and then brine, dried (Na 2 S0 4 ), filtered and concentrated under reduced pressure. IH NMR (300 Milky CDCI ) 6 7L65-7.55 Hz, IH), 5.22 (s, 2H), 5.16 (s, 2H). ESHRMS m/z 424.0159 (M+H C 19 HI 4 BrF 3 N0 2 requires 424.0155). Example 108 F 3-Bromo-l-(3-fluorobenzyl)-4-(2,3,4-trifluorobenzyloxy)-iHpyridin-2-one The title compound was prepared by a procedure similar to the one described for Example 107 (0.09 g, 39%): mp 176-178 °C; IH NMR (300 MHz, CDCI 3 ) 6 7.40-7.25 (m, 4H), 7.11-6.98 (m, 4H), 6.11 (d, J = 9 Hz, IH), 5.23 (s, 2H), 5.16 (s, 2H). ESHRMS m/z 442.0060 (M+H C 19 HI 3 BrF 4 NO 2 requires 442.0061).. Example 109 O.. NH 2 O l-[3-(2-Aminoethyl) benzyl]-3-bromo-4-(2,4-difluorobenzyloxy)- iH-pyridin-2-one The title compound was prepared from compound of Example 97 by a procedure similar to the one described for Example 99, as the TFA salt (0.13 g, 33%): mp 70-74 °C; IH NMR (300 MHz, DMSOd 6) 6 8.21 (br s, IH), 6.60-6.50 (m, IH), 7.52 (d, J = 6 Hz, IH) , 7.30-7.10 (m, 3H) , 7.01 (d, J = 9 Hz, IH) , 6.94-6.85 (m, 2H), 6.20 (d, J = 6 Hz, IH), 5.20 (s, 2H), 5.05 (s, 2H), 3.23 (br s, 2H), 2.97 (t, J = 8 Hz, 2H), 2.05 (br s, 2H). ESHRMS m/z 449.0698 (M+H CnH 20 BrF 2 N 2 0 2 requires 449.0671). Example ii0 3-Chloro-4-(2,4-difluorobenzyloxy)-l-(3-fluorobenzyl)-IHpyridin-2-one Step I. Preparation of 4-(2,4-difluorobenzyloxy)-l-(3fluorobenzyl)-iH~pyridin-2-one. To a solution of l-(3-fluorobenzyl)-4-hydroxy-iH-pyridin-2-one (from Step 2 EXAMPLE 107) (0.92 g, 4.2 mmol) and K 2 C0 3 (1.2 g, 8.4 mmol) in acetone (62 mL) was added 2,4-difluorobenzyl bromide (1.3 g, 6.3 mmol), and the reaction mixture was heated at reflux for 3 h. The reaction mixture was cooled room temperature, concentrated under reduced pressure, and the residue was partitioned between water and EtOAc. The organic solution was washed with brine, dried (Na SO 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 95 : 5 methylene chloride/methanol) to provide 4- (2,4difluorobenzyloxy) -I- (3-fluorobenzyl)-iH-pyridin-2-one as a white solid (1.21 g, 84%): IH NMR (300 MHz, CDCI 3 ) 6 7.45-7.20 (m, 2H), 7.14 (d, J = 8 Hz, IH), 7.05-6.75 (m, 5H), 6.05 (d, J = 3 Hz, IH), 5.95 (dd, J = 5, 3 Hz, IH), 5.08 (s, 2H), 5.00 (s, 2H). Step 2. Preparation of 3-Chloro-4-(2,4-difluorobenzyloxy)-l- (3-fluorobenzyl)-iH-pyridin-2-one. To a solution of 4-(2,4-difluorobenzyloxy)-l-(3-fluorobenzyl)- iH-pyridin-2-one (0.15 g, 0.4 mmol) in AcOH (3 mL) was added N-chlorosuccinimide (70 mg, 0.5 mmol), and the reaction mixture was heated at reflux for i0 min. The reaction mixture was cooled room temperature and the solvent was removed under reduced pressure. IH NMR (300 MHz, CDCI 3 ) 6 7.60-7.50 (m, IH) , 7.45-7.20 (m, 2H) , 7.10-6.80 (m, 5H), 6.16 (d, J = 8 Hz, IH) , 5.21 (s, 2H) , 5.15 (s, 2H) . ESHRMS m/z 380.0641 (M+H C 19 HI 4 CIF 3 N0 2 requires 480.0660). Examples ili-123 The following example compounds were prepared by procedures similar to that described for Example 107. The yields and the analytical data are described below. Example iii 3-Bromo-4-(3-chlorobenzyloxy)-l-(3-fluorobenzyl)-iH-pyridin-2one The title compound was prepared by a procedure similar to the one described for EXAMPLE 107 (0.12 g, 42%): mp 149-153 °C; IH NMR (300 MHz, CDCI 3 ) 6 7.40-7.23 (m, 6H), 7.09 (d, J = 8 Hz, IH), 7.05-6.95 (m, 2H), 6.05 (d, J = 8 Hz, IH), 5.19 (s, 2H) , 5.14 (s, 2H) . ESMS m/z M+H 442. Example I12 BrO F 3-Bromo-4-(3,4-difluorobenzyloxy)-l-(3-fluorobenzyl)-iHpyridin-2-one The title compound was prepared by a procedure similar to the one described for EXAMPLE 107 (0.08 g, 48%): mp 172-174 °C; IH N-MR (300 MHz, CDCI 3 ) 6 7.40-6.95 (m, 8H), 6.05 (d, J = 6 Hz, IH), 5.16 (s, 4H) . ESHRMS m/z 424.0111 (M+H C 19 HI 4 BrF 3 NO 2 requlres 424.0155). Example 113 F F O 3-Bromo-l-(3-fluorobenzyl)-4-(4-fluorobenzyloxy)-iH-pyridin-2one The title compound was prepared by a procedure similar to the one described for EXAMPLE 107 (0.07 g, 35%): mp 180-183 °C; IH NMR (300 MHz, CDCI 3 ) 6 7.50-7.25 (m, 5H) , 7.15-7.00 (m, 4H) , 6.07 (d, J = 8 Hz, IH), 5.18 (s, 2H), 5.14 (s, 2H). ESHRMS m/z 406.0258 (M+H C 19 HIsBrF NO 2 requires 406.0249). Example 114 3-Bromo-l-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)-IH-pyridin-2one To an ice-cold solution of l-(3-fluorobenzyl)-4-(3fluorobenzyLo -y)-iH-pzridin-2-one (0.14 g, 0.43 mmol) in AcOH (2 mL) wa dded a saiutio of bromine (72 mg, 0.45 mm l) in AcOH (I mL), and the reaction mixture was stirred for 5 min. The reaction mixture was warmed to room temperature and the solvent was removed under reduced pressure. IH NMR (300 MHz, CDCI ) 6 7.45-6.95 (m, 9H), 6.05 (d, J = 8 Hz, IH), 5.21 (s, 2H), 5.14 (s, 2H) . ESHRMS m/z 406.0254 (M+H CI HIsBrF 2 NO 2 requires 406.0249). Examples 115-123 The compounds of Examples 115-123 are prepared essentially according to the procedures set forth above for Example 107: O M+H ESHRMS Example No. R MF Requires m/z Ex. 115 3-methoxy 418. 0449 1 418. 0427 Z 20 HIvBrFN0 3 Ex. 116 4-tern-butyl C 23 H 2 BrFN0 2 444.0969444.0977 Ex. 117 3-methyl C 20 H!vBrFNO 2 402.0499402.0513 Ex. 118 4trifluoromethyl C 20 HI 4 BrF 4 NO 2 456.0217456.021¢ Ex. 119 4-cyano C 20 HI 4 BrFN 2 0 2 413.0295 413.0313 Ex. 120 2-methyl C 20 HIvBrFN0 2 402.0499402.050 Ex. 121 12-phenyl C 2 sHIgBrFNO 2 464.0656464.0654 Ex. 122 4-methoxy C 20 HITBrFN0 3 418.0449418.045£ Ex. 123 2-CO 2 CH 3 C 21 HI 7 BrFN0 4 446.0398 446.0402 N-MR characterization of compounds of Examples I15-123 Example I NMR Data Example 124 3-Bromo-l-(3-fluorobenzyl)-4-(2-hydroxymethylbenzyloxy)-IHpyridin-2-one Step i. Preparation of 3-Bromo-l-(3-fluorobenzyl)-4-(2hydroxymethylbenzyloxy)-IH-pyridin-2-one. To an ice-cold solution of methyl 2-[3-bromo-l-(3fluorobenzyl)-2-oxo-l,2-dihydro-pyridin-4-yloxymethyl]benzoate (0.12 g, 0.28 retool) in THF (5 mL) was added LiBH 4 (0.15 mL of 2.0 M solution in THF, 0.30 mmol), and the reaction mixture heated at reflux for 5 hours. The reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue dissolved in EtOAc. The organic solution was washed with brine, dried (Na 2 SO 4 ), filtered, and concentrated under reduced pressure. IH NMR (300 MHz, DMSO-d ) 6 7.98 (d, J = 8 Hz, IH), 7.46-7.28 (m, 5H), 7.15-7.10 (m, 3H), 6.56 (d, J = 8 Hz, IH) , 5.35 (s, 2H), 5.25 (br s, IH), 5.14 (s, 2H). ESHRMS m/z 418.0453 (M+H C 20 HIsBrFNO 3 requires 418.0449). Example 126 Br O H 2 NOC J 2-(2- [3-Bromo-4- (2,4-difluorobenzyloxy) -2-oxo-2H-pyridinl- ylmethyl] -phen¥1 } acetamide Step I. Preparation of (2-Bromomethylphenyl)acetic acid. A solution of isochroman-3~one (1.5 g, i0 mmol) in 30% HBr in acetic acid (13 niL) was stirred at room temperature for 2 h, and 70 °C for 1 h. The reaction mixture was cooled to room temperature, and poured into ice-water. The precipitate was collected to afford (2-bromomethylphenyl)acetic acid as an off-white solid (2.15 g, 93%) : iH NMR (300 MHz, DMSO-d 6 ) 6 7.45-7.23 (m, 4H) , 4.73 (s, 2H) , 3.73 (s, 2H) . Step 2. Preparation of Methyl (2-Bromomethylphenyl)acetate. To an ice-cold solution of (2-bromomethylphenyl)acetic acid (I g, 4.4 mmol) in THF (2.4 mL) was added trimethylsilyldiazomethane (3 mL of a 2 M solution in hexanes, 6 mmol), and the reaction mixture was stirred for 14 h. The reaction was quenched with AcOH, and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, eluent 98:2 to 94:6 methylene chloride/hexanes) afforded methyl (2-bromomethylphenyl)acetate as a light yellow solid (0.34 g, 32%): IH NMR (300 MHz, CDCI 3 ) 6 7.40-7.20 (m, 4H), 4.59 (s, 2H), 3.81 (s 2H), 3.71 (s, 3H) . Step 3. Preparation of Methyl {2- [3-bromo-4- (2,4di f luorobenzyloxy) -2 -oxo2H-pyridin1 -ylmethyl ] phenyl } acetate. Methyl {2- [3-bromo-4- (2,4-difluorobenzyloxy)-2-oxo-2H-pyridinl-ylmethyl]-phenyl}acetate was prepared by a procedure similar to the one described for EXAMPLE 74 (0.41 g, 68%): IH NMR (300 MHz, CDCI 3 ) 6 7.55-6.81 (m, 8 H) , 6.10 (d, J = 6 Hz, IH) , 5.20 (s, 4 H), 3.78 (s, 2H), 3.60 (s, 3H) . Step 4. Preparation of 2- {2- [3-Bromo-4- (2,4di f luorobenzyloxy) -2 -oxo2H-pyridinl- ylmethyl ] phenyl } acetamide. 2- { 2- [3-Bromo-4- (2,4-difluorobenzyloxy) -2-oxo-2H-pyridin-lylmethyl]phenyl}-acetamide was prepared by a procedure similar to the one described for Example 102 (0.07 g, 72%): mp 178183 °C; IH NMR (300 MHz, DMSO-d 6 ) 6 7.89 (d, J = 8 Hz, IH), 7.66 (d, J = 9 Hz, 1 H), 7.54 (br s, IH), 7.35 (br s, IH), 7.30-7.15 (m, 4H) , 6.98 (br s, IH) , 6.85 (d, J = 7 Hz, IH) , 6.60 (d, J = 8 Hz, IH), 5.32 (s, 2H) , 5.19 (s, 2H) , 3.62 (s, 2H) . ESHRMS m/z 463.0442 (M+H CnHIsBrF 2 N 2 0 requires 463.0463). Example 127 Ethyl {3-[3-Bromo-4-(2,4-difluorobenzyloxy)-2-oxo-2H-pyridinl-ylmethyl]-phenyl}acetate Step i. Preparation of Ethyl (3-bromomethylphenyl) acetate. To a mixture of m-tolylacetic acid ethyl ester (3.0 g, 16.8 mmol) and N-bromosuccinimide (3.0 g, 16.8 mmol) was added carbon tetrachloride (45 mL), followed by benzoyl peroxide (5 mg), and the reaction mixture was heated at reflux for 16 h. The reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 5:95 to 2:3 EtOAc/hexanes) afforded ethyl (3-bromomethylphenyl) acetate as an off-white solid (0.89 g, 21% ) : IH NMR (300 MHz, CDCI 3 ) 6 7.32-7.21 (m, 4H), 4.48 (s, 2H), 4.16 (q, J = 6 Hz, 2H), 3.63, (s, 2H), 1.27 (t, J = 6 Hz, 3H). Step 2. Preparation of Ethyl {3- [3-Bromo-4-(2,4difluorobenzyloxy)-2-oxo-2H-pyridin-l-ylmethyl]phenyl}acetate. Ethyl {3-[3-Bromo-4-(2,4-difluorobenzyloxy)-2-oxo-2H-pyridinl-ylmethyl]phenyl}-acetate was prepared by a procedure similar to the one described for EXAMPLE 74 (0.27 g, 69%) : mp 95-98 = 6 HZ, 3H). ESHRMS m/z 492.0655 (M+H C 23 H 21 BrP 2 NO 4 requires 435.0617). Example 128 F O O Br NY NH 2 O 2-{3-[3-Bromo-4-(2,4-difluorobenzyloxy)-2-oxo-2H-pyridin-lylmethyl] phenyl) acetamide The title compound was prepared by a procedure similar to the one described for EXAMPLE 102 (0.07 g, 28%): mp 164-167 °C; NMR (300 MHz, DMSO-d ) 6 7.96 (d, J = 9 Hz, IH), 7.70-7.60 (m, IH), 7.60 (br s, IH), 7.50-7.10 (m, 6H), 6.89 (br s, IH), 6.58 (d, J = 9 Hz, IH), 5.31 (s, 2H), 5.12 (s, 2H), 3.32 (s, 2H). ESHRMS m/z 463.0485 (M+H CnHIsBrF 2 N 2 0 requires 463.0464). Example 129 O 4-(2,4-Difluorobenzyloxy)-l-(3-fluorobenzyl)-3-methyl-iHpyridin-2-one Step I. Preparation of 4- (2,4-Difluorobenzyloxy)-l- (3fl uorobenzyl ) - 3 -methyl - 1 Hpyridin - 2 - one. To a solution of 3-bromo-4- (2,4-difluorobenzyloxy)-l-(3fluorobenzyl) -is-pyridin-2-one (EXAMPLE 107) (0.14 g, 0.32 retool), K 2 CO 3 (88 rag, 0.64 retool) and CszC0 3 (0.10 g, 0.32 retool) in dioxane (2 mL) was added Pd(PPh 3 ) 4 (18 rag, 0.12 retool), followed by trimethylboroxine (40 mg, 0.32 mmol). The reaction mixture was degassed, purged with argon, and heated at reflux for 4 h. The reaction mixture was cooled to room temperature, and partitioned between water and EtOAc. The organic solution was washed with brine, dried (Na 2 SO 4 ), filtered and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 97:3 methylene chloride/MeOHJ afforded 4-(2,4- difluorobenzyloxy) -I- (3fluorobenzyl) - 3-methyliH-pyridin-2one as a white solid (0.09 g, 79% ) :mp 127-129 °C; IH NMR (300 MHz, CDCI 3 ) 6 7.50-7.40 (m, IH), 7.35-7.25 (m, IH), 7.17 (d, J = 9 Hz, IH) , 7.06 (d, J = 6 Hz, IH) , 7.00-6.80 (m, 4H) , 6.12 (d, J = 9 Hz, IH) , 5.12 (s, 4H) , 2.07 (s, 3H) . ESHRMS m/z 360.1180 (M+H C 20 HI F 3 N0 2 requires 360.1206). Example 130 F 4-(2,4-Difluorobenzyloxy)-l-(3-fluorobenzyl)-3-iodo-IHpyridin-2-one Step 1. Preparation of 4-(2,4-Difluorobenzyloxy)-l-(3i uorobenzyl)-iH-pyridin-2-one. To a mixture of l-(3-fluorobenzyl)-4-hydroxy-IH-pyridin-2-one (from Step I, EXAMPLE ii0) (0.92 g, 4.2 mmol) and K 2 C0 3 (1.15 g, 8.4 mmol) in acetone (62 mL) was added 2,4-difluorobenzyl bromide (1.3 g, 6.3 mmol), and the reaction mixture was heated at reflux for 3 h. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and the residue was dissolved in EtOAc. The organic solution was washed with water and then brine, dried (Na 2 SO 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 95:5 methylene chloride/methanol) provided 4-(2,4difluorobenzyloxy)-l-(3-fluorobenzyl)-iH-pyridin-2-one as a white solid (1.21 g, 84%): IH NMR (300 MHz, CDCI 3 ) 6 7.45-7.20 (m, 2H), 7.14 (d, J = 8 Hz, IH), 7.05-6.75 (m, 5H), 6.05 (d, J = 3 Hz, IH), 5.95 (dd, J = 5, 3 Hz, IH) , 5.08 (s, 2H), 5.00 (s, 2H). Step 2. Preparation of 4-(2,4-Difluorobenzyloxy)-l-(3fluorobenzyl)-3-iodo-iH-pyridin-2-one. To a mixture of 4-(2,4-difluorobenzyloxy)-l-(3-fluorobenzyl)- IH-pyridin-2-one (0.15 g, 0.43 mmol) and N-iodosuccinimide (0.I0 g, 0.46 mmol) in CHHCN (3 mL) was added dichloroacetic acid (13 mg, 0.i0 mmol), and the reaction mixture was heated to 60 °C for 4 h. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and the residue was dissolved in methylene chloride. The organic solution was washed with a saturated solution of NaHCO and then brine, dried (Na 2 S0 4 ), filtered and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 90:10 methylene chloride/hexanes to 99:1 methylene chloride/methanol) provided 4-(2,4difluorobenzyloxy)-l-(3-fluorobenzyl)-3-iodo-iH-pyridin_2_one as a white solid (0.15 g, 77%) : mp 164-167 °C; IH NMR (300 MHz, ESHRMS m/z 472.0033 (M+H CIgHI 4 F INO 2 requires 472.0018). Example 131 F 4- (2,4-Difluorobenzyloxy) -I- (3-fluorobenzyl) -2-oxo-l, 2dihydropyridine3 - carboni tri le Step I. Preparation of 4-Methoxy-2-oxo-l,2-dihydropyridine-3carbonitrile. A solution of 2-(dimethylaminoethoxymethylene)malononitrile (1.97 g) in concentrated sulfuric acid (7.0 mL) was stirred at room temperature for 6.5 h. The reaction mixture was poured into water, and the precipitate was collected by filtration. IH NMR (300 MHz, DMSO-d 6 ) 6 12.14 (br s, IH) , 7.79 (d, J = 9 Hz, IH), 6.35 (d, J = 9 Hz, IH), 3.98 (s, 3H) . Step 2. Preparation of i-(3-Fluorobenzyl)-4-methoxy-2-oxoi, 2 - dihydro-pyridine3 - carboni tri i e. 1 - ( 3 - Fluorobenzyl ) - 4 - met hoxy2 -oxoI, 2 - dihydro -pyridine - 3 - carbonitrile was prepared by a procedure similar to the one described for EXAMPLE 74 (0.56 g, 93%): IH NMR (300 MHz, CDCI ) 7.48 (d, J = 9 Hz, IH), 7.40-7.27 (m, IH) , 7.00-6.95 (m, 2H), 6.08 (d, J = 9 Hz, IH), 5.10 (s, 2H), 4.00 (s, 3H) . Step 3. Preparation of i- (3-Fluorobenzyl)-4-hydroxy-2-oxo1,2-dihydropyridine-3-carbonitrile. To a solution of sodium hydride (92 mg of a 60% dispersion in mineral oil, 2.3 mmol) in DMF (7 mL) was added ethanethiol (0.14 g, 2.2 mmol), followed by a solution of 1-(3fluorobenzyl)-4-methoxy-2-oxo-l,2-dihydropyridine-3carbonitrile (0.23 g, 0.89 mmol) in DMF (2 mL), and the reaction mixture was heated to i00 °C. The reaction mixture was cooled to room temperature, acidified with 3 N HCI, and washed with EtOAc. The organic solution was washed with brine, dried (Na 2 SO 4 ), filtered and concentrated under reduced pressure to give l-(3-fluorobenzyl)-4-hydroxy-2-oxo-l,2dihydro-pyridine-3-carbonitrile as an off-white solid (0.20 g, 91%) : IH NMR (300 MHz, MeOD) 6 8.00 (s, IH), 7.82 (d, J = 8 Hz, IH), 7.40-7.30 (m, IH), 7.15-7.00 (m, 2H), 6.13 (d, J = 8 Hz, IH), 5.11 (s, 2H) . Step 4. Preparation of 4-(2,4-Difluorobenzyloxy)-l-(3fluorobenzyl)-2-oxo-l,2-dihydro-pyridine-3-carbonitrile. 4~(2,4-Difluorobenzyloxy)-l-(3-fluorobenzyl)-2-oxo-l,2dihydro-pyridine-3-carbonitrile was prepared by a procedure similar to the one described for EXAMPLE 107 (0.09 g, 30%): mp 187-190 °C; iH NMR (300 MHz, CDCI 3 ) 6 7.60-7.45 (m, 2H), 7.407.30 (m, IH), 7.10-6.50 (m, 5H) , 6.13 (d, J = 9 Hz, IH) , 5.27 (s, 2H), 5.10 (s, 2H) . Example 132 l-Cyclohexyl-4-(2,4-difluorobenzyloxy)-3,6-dimethyl-iHpyridin-2-one Step 1. Preparation of Methyl l-cyclohexyl-4-hydroxy-2,5- dimethyl-6-oxo-l,6-dihydro-pyridine-3-carboxylate. To a solution of 3-cyclohexylaminobut-2-enoic acid methyl ester (1.12 g, 5.72 mmol) in bromobenzene (20 niL) was added 2methylmalonic acid bis-(2,4,6-trichloro-phenyl) ester (2.71 g, 5.72 mmol)and the reaction mixture was heated at 170 °C for 3 h. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 94:6 methylene chloride/MeOH) and recrystallization from hot MeOH provided methyl l-cyclohexyl-4-hydroxy-2,5-dimethyl-6- oxo-l,6-dihydropyridine-3-carboxylate as pale yellow crystals (0.34 g, 21%) : IH NMR (500 MHz, DMSO-dG) 9.82 (s, IH), 4.003.90 (m, IH), 3.76 (s, 3H), 2.75-2.60 (m, 2H), 2.31 (s, 3H), 1.81 (s, 3H), 1.80-1.70 (m, 2H), 1.65-1.50 (m, 3H), 1.40-1.20 (m, 2H) , 1.15-1.05 (m, IH) . Step 2. Preparation of l-Cyclohexyl-4-hydroxy-2,5-dimethyl-6oxo-l,6-dihydro-pyridine-3-carboxylic acid. A solution of methyl l-cyclohexyl-4-hydroxy-2,5-dimethyl-6oxo-l,6-dihydro-pyridine-3-carboxylate (0.35 g, 1.25 mmol) in 2 N NaOH (5 mL) was heated at reflux for 3.5 h. The reaction mixture was cooled room temperature, acidified to pH 1-2 with 1 N HCI, and washed with EtOAc. The organic solution was washed with brine, dried (MgS0 4 ), filtered and concentrated under reduced pressure to afford l-cyclohexyl-4-hydroxy-2,5dimethyl-6-oxo-l,6-dihydropyridine-3-carboxylic acid as a white solid (0.31 g, 94%) : IH NMR (300 MHz, MeOD) 6 4.30-4.00 Step 3. Preparation of l-Cyclohexyl-4-hydroxy-3,6-dimethyliH-pyridin-2-one. A solution of l-cyclohexyi-4-hydroxy-2,5-dimethyl-6-oxo-l,6dihydropyridine-3-carboxylic acid (0.15 g, 0.57 mmol) in concentrated HCI (5 niL) was heated at reflux for 4 h. The reaction mixture was cooled to room temperature, diluted with water and washed with EtOAc. The organic solution was washed with brine, dried (MgSO 4 ), filtered and concentrated under reduced pressure to give l-cyclohexyl-4-hydroxy-3,6-dimethyliH-pyridin-2-one as a white solid (0.2 g, 77%) : IH NMR (300 MHz, DMSO-d ) 6 9.81 (s, IH), 5.73 (s, IH), 3.95-3.75 (m, IH), 2.80-2.55 (m, 2H), 2.25 (s, 3H), 1.85-1.40 (m, 5H), 1.72 (s, 3H), 1.38-1.05 (m, 3H) . Step 4. Preparation of l-Cyclohexyl-4~(2,4difluorobenzyloxy)-3,6-dimethyl-IH-pyridin-2-one. l-Cyclohexyl-4-(2,4-difluorobenzyloxy)-3,6-dimethyl-iHpyridin-2-one was prepared by a procedure similar to the one described for EXAMPLE 107 (0.05 g, 16%): mp 118-120 °C; IH NMR (300 MHz, CDCI 3 ) 6 7.48-7.41 (m, IH), 6.95-6.81 (m, 2H), 5.87 (s, IH), 5.07 (s, 2H), 4.05-3.85 (m, IH), 3.00-2.80 (m, 2H), 2.35 (s, 3H), 1.98 (s, 3H), 1.95-1.80 (m, 2H), 1.70-1.55 (m, 3H), 1.40-1.20 (m, 3H). Example 133 3-Chloro-4-(2,4-difluorobenzyloxy)-6-methyl-l-(IH-pyrazol-4_ ylmethyl)-iH-pyridin-2-one Step i. Preparation of 4-Methylpyrazole-l-carboxylic acid tert-butyl ester. To a solution of 4-methyl-is-pyrazole (i g, 12 mmol) and DMAP (0.15 g, 1.2 mmol) in CH 3 CN (20 mL) was added di-tert-butyl dicarbonate (2.8 g, 13 mmol), and the reaction mixture was stirred for 1 h. The reaction mixture was concentrated under reduced pressure, and the residue dissolved in EtOAc. The organic solution was washed with 1 N HCI, water and then brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure to provide 4-methyl-pyrazole-l-carboxylic acid tertbuty! ester as a light yellow oil (2.2 g, 100%): IH NMR (300 MHz, CDCI 3 ) 6 7.83 (s, IH) , 7.53 (s, IH) , 2.09 (s, 3H) , 1.64 (s, 9H). Step 2. Preparation of 4-Bromomethylpyrazole-l-carboxylic acid tert-butyl ester. To a solution of 4-methylpyrazole-l-carboxylic acid tert-butyl ester (i.0 g, 5.5 mmol) in carbon tetrachloride (20 mL) was added N-bromosuccinimide (i.0 g, 5.6 mmol) and benzoyl peroxide (50 mg), and the reaction mixture was heated at reflux for 16 h. The reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:4 EtOAc/hexanes) provided 4-bromomethylpyrazole-lcarboxylic acid tert-butyl ester as a light yellow oil (0.42 Step 3. Preparation of 4-[3-Chloro-4-(2,4-difluorobenzyloxy)- 6-methyl-2-oxo-2H-pyridin-l-ylmethyl]pyrazole-l-carboxylic acid tert-butyl ester. 4-[3-Chloro-4-(2,4-difluorobenzyloxy)-6-methyl-2-oxo-2Hpyridin-!-ylmethyl]pyrazole-l-carboxylic acid tert-butyl ester was prepared by a procedure similar to the one described for EXAMPLE 632: IH NMR (300 MHz, CDCI 3 ) 6 8.09 (s, IH), 7.72 (s, IH), 7.53 (app q, J = 6 Hz, IH), 6.97-6.82 (m, 2H), 6.00 (s, IH) , 5.19 (s, 2H) , 5.13 (s, 2H), 2.43 (s, 3H), 1.63 (s, 9H) . Step 4. Preparation of 3-Chloro-4-(2,4-difluorobenzyloxy)-6methyl-l-(iH-pyrazol-4-ylmethyl)-IH-pyridin-2-one. 4-[3-Chloro-4-(2,4-difluorobenzyloxy)-6-methyl-2-oxo-2Hpyridin-l-ylmethyl]pyrazole-l-carboxylic acid tert-butyl ester (0.16 g, 0.34 mmol) was heated to 140 °C for 16 h. The reaction mixture was cooled to room temperature. IH NMR (300 MHz, CDCI 3 ) 6 8.33 (s, 2H), 7.68 (d, J = 6 Hz, IH), 7.52 (app q, J = 6 Hz, IH), 6.93-6.83 (m, 2H), 6.47 68 (d, J = 9 Hz, IH), 5.19 (s, 2H), 5.24 (s, 2H), 5.20(s, 2H). Example 134 4-( [4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]methyl)benzonitrile Preparation of 4-{[4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]methyl}benzonitrile. 3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methylpyridin-2(1H)-one(l.0 g, 3.6 mmol) was dissolved in N,N-dimethylformamide (5 mL) . -Bromo-p-tolunitrile (0.85g, 4.3 mmol) was added followed by K 2 C0 3 (0.59 9, 4.3 mmol) . The resulting mixture was heated to 80 °C for 16 h. The reaction was concentrated to an oil that was partitioned between water and ethyl acetate and extracted with ethyl acetate (3 x I00 ml). The organic extracts were combined, washed with brine, dried over Na 2 S0 4 , and filtered. The filtrate was concentrated to an oil, and purified by chromatography (silica ge!, hexane/ethyl acetate) to yield a white solid (0.65 g, 46%). IH NMR (400 MHz, CDCI 3 ) 6 7.62 (d, J = 8.4 Hz, 2H), 7.41-7.31 (m, 7H), 7.23 (d, J = 7.6 Hz, IH), 6.11 (d, J = 8.0 Hz, IH), 5.24 (s, 2H), 5.18 (s, 2H). ES HRMS m/z 395.0404 (M+H C 20 HIsBrN 2 0 2 requires 395.0390). Example 135 3-{ [4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]methyl}benzonitrile O The title compound was prepared by a procedure essentially as described in example 134.1H NMR (400 MHz, CDCI 3 ) 6 7.62-7.54 (m, 3H), 7.45 (d, J = 7 Hz, IH), 7.43-7.31 (m, 5H), 7.26 (d, J = 1.6 Hz, IH), 6.12 (d, J = 1.6 Hz, IH), 5.24 is, 2H), 5.15 (s, 2H) . ES HRMS m/z 395.0420 (M+H C 20 H 1 sBrN 2 0 2 requires Example 136 2-{ [4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]methyl}benzonitrile N O The title compound was prepared by a procedure essentially as described in example 134. IH NMR (400 MHz, CDCI 3 ) 6 7.74 (d, J = 8.4 Hz, IH) ; 7.63 (dd, J = 1.2, 8.0 Hz, IH), 7.57 (dr, J = 1.2, 8.4 Hz, IH), 7.55 (d, J = 8.0 Hz, IH) ; 7.43-7.30 (m, 6H) , 6.13 (d, J = 8.0 Hz, IH,), 5.33 (s, 2H), 5.23 (s, 2H) . ES HRMS m/z 395.0398 (M+H C 20 HIsBrN 2 0 2 requires 395.0390). Example 137 l-[4-(aminomethyl)benzyl]-4-(benzyloxy)-3-bromopyridin-2(iH)- one O H 2 N Preparation of l-[4-(aminomethyl)benzyl]-4-(benzyloxy)-3bromopyridin-2(iH)-one. EXAMPLE 134 (i00 mg, 0.25 mmol) was dissolved in tetrahydrofuran (2 mL) under N 2 . Borane dimethylsulfide complex (0.25 mL, 0.Smmol, 2M in tetrahydrofuran) was added. The reaction was then heated to 70"C and shaken overnight. The mixture was cooled and all the solvent was distilled under vacuum. The resulting residue was partitioned between ethyl acetate and 0.2 N NaOH, and extracted with ethyl acetate (3 x I0 mL) . The organic extracts were combined, washed with brine, dried over Na 2 SO 4 , and filtered. The filtrate was concentrated to an oil, and triturated with dichloromethane and hexane to give an offwhite solid. (80 rag, 80%). IH NMR (400 MHz, dGDMSO) 6 7.90 (d, J = 7.6 Hz, IH) ; 7.43-7.21 (m, 9H), 6.70 (d, J=7.6 Hz, IH), 5.29 (s, 2H), 5.08 (s, 2H), 3.71 (s, 2H) . ES HRMS m/z 399.0721 (M+H C 20 HIgBrN 2 0 2 requires 399.0703). Example 138 I- [3- (aminomethyl)benzyl] -4- (benzyloxy) -3-bromopyridin-2 (IH) - one Br ,NH 2 The title compound was prepared by a procedure essentially as described in Example 137 using the title compound of Example 135 as starting material, iH NMR (400 MHz, d 6 DMSO) 6 7.90 (d, J = 7.6 Hz, IH) , 7.44-7.22 (m, 9H) , 6.50 (d, J=7.6 Hz, IH), 5.30 (s, 2H), 5.12 (s, 2H), 3.88 (s, 2H) . ES HRMS m/z 399.0730 (M+H C 20 HIgBrN 2 0 2 requires 399.0703). Example 139 l-[2-(aminomethyl)benzyl]-4-(benzyloxy)-3-bromopyridin-2(IH)- one O The title compound was prepared by a procedure essentially as described in Example 137 using the title compound of Example 136 as starting material.iH NMR (400 MHz, d 6 DMSO) 6 7.88 (d, J = 8.0 Hz, IH) ; 7.45-7.34 (m, 5H), 7.267.21 (m, 3H) ; 6.85 (d, J=7.2 Hz, IH), 6.53 (d, J=7.6 Hz, IH), 5.32 (s, 2H), 5.12 (s, 2H), 3.90 (s, 2H) . ES HRMS m/z 399.0699 (M+H C 20 HIgBrN 2 0 2 requires 399.0703). Example 140 4-{ [4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]methyl}benzamide O H 2 N Preparation of 4-{ [4- (benzyloxy)-3-bromo-2-oxopyridin~l (2H)- yl]methyl}benzamide. EXAMPLE 134 (I00 mg, 0.25 mmol) was added to a suspension of potassium fluoride (40% on alumina) in tbutyl alcohol, heated to 85"C, and stirred for 20h. The alumina was removed by filtration and washed with dichloromethane and water. The resulting filtrate was separated and the aqueous layer was extracted with dichloromethane (2 x 20 mL). The organic extracts were combined, dried over Na 2 SO 4 , and filtered. The filtrate was concentrated to an oil. Trituration with dichloromethane hexane gave a solid (11.5 rag, 11%). IH NMR (400 MHz, d DMSO) 7.94 (d, J = 8.0 Hz, IH), 7.80 (d, J = 8.4 Hz, 2H); 7.43-7.29 (m, 7H), 6.51 (d, J=7.6 Hz, !H), 5.31 (s, 2H), 5.16 (s, 2H). ES HRMS m/z 413.0541 (M+H C 20 HITBrN 2 0 3 requires 413.0495). Example 141 3-{[4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]methyl}benzamide O O The title compound was prepared by a procedure essentially as described in Example 140 using the title compound of Example 135 as starting material. IH NMR (400 d 6 DMSO) 6 7.95 (d, J = 7.6 Hz, 2H), 7.76 (m, 2H); 7.43-7.26 8H), 6.51 (d, J=7.6 Hz, IH), 5.31 (s, 2H), 5.15 (s, 2H). ESHRMS m/z 413.0497 (M+H C 20 HIvBrN 2 0 requires 413.0495). Example 142 2-{[4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]methyl}benzamide The title compound was prepared by a procedure essentially as described in Example 140 using the title compound of Example 136 as starting material. IH NMR (400 MHz, d 6 DMSO) 6 7.78 (d, J = 7.6 Hz, IH), 7.54 (dd, J = 1.6, 7.6 Hz, IH) ; 7.45 (d, J=7.6 Hz, 2H) ; 7.44-7.32 (m, 5H), 7.15 (d, J=7.6 Hz, IH), 6.49 (d, J=7.6 Hz, IH), 5.39 (s, 2H), 5.30 (s, 2H) . ES HRMS m/z 4413.0506 (M+H C 20 HITBrN 2 0 3 requires 413.0495). Example 143 Methyl 3-{ [4- (benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl] methyl }benzoate O O Preparation of Methyl 3-{ [4-(benzyloxy)-3-bromo-2-oxopyridinl(2H)-yl]methyl}benzoate. EXAMPLE 134 (I00 mg, 0.25 mmol) was suspended in methanol and cooled to 0"C. HCI (g) was bubbled through the mixture until saturated (-30 minutes). The reaction was warmed to ambient temperature and stirred for 4 hours. HCI and methanol were removed in vacuo, yielding an oil, that was purified by chromatography (silica gel, hexane/ethyl acetate) to yield a white solid (3 mg, 3%). IH NMR 3.88, (s, 3H). API-ES MS m/z 429.0 (M+H C 21 HIsBrN0 4 requires 428.0492). Example 144 Methyl 4-{ [4- (benzyloxy)-3-bromo-2-oxopyridin-I (2H) - yl] methyl }benzoate The title compound was prepared by a procedure essentially as described in Example 143 using the title compound of Example 134 as starting material. IH NMR (400 MHz, CD 3 OD) 6 7.94 (app d, J = 8.4 Hz, 2H), 7.76 (app d, J = 7.6 Hz, IH) ; 7.46 (app J = 8.0 Hz, 2H) ; 7.39-7.35 (m, 5H) , 6.51 (d, J=7.6 Hz, IH) , 5.31 (s, 2H), 5.26 (s, 2H) ; 3.88, (s, 3H) . ES HRMS m/z 428.0492 (M+H C 21 HIsBrNO 4 requires 428.0492). Example 145 4- [4- (benzyloxy) -3-bromo-2-oxopyridin-i (2H) -yl ] benzonitrile O Preparation of 4-[4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]benzonitrile 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(iH)-one(100 mg, 0.36 mmol) was suspended in dimethylsulfoxide (5 mL), cesium carbonate (375 mg, 1.15 mmol) was added and the reaction was shaken for 5 minutes. 4Fluorobenzonitrile (52 mg, 0.43 mmol was then added, the reaction was heated to 80"C, and stirred. Reaction was monitored by LC/MS, and after 4h was heated to 100'C and stirred for 16 hours. Reaction mixture was partitioned between water and ethyl acetate and extracted with ethyl acetate (5 x 50 mL) . The organic extracts were combined, washed with brine, dried over Na 2 SO 4 , and filtered. The filtrate was concentrated to an oil, and purified by chromatography (silica gel, hexane/ethyl acetate) to yield a white solid (40 rag, 29%). iH NMR (400 MHz, CDCI 3 ) 6 7.77 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.8 Hz, 2H), 7.44-7.42 (m, 4H), 7.28 (d, J = 7.6 Hz, IH), 7.26 (s, IH), 6.24 (d, J = 7.6 Hz, IH) ; 5.31, (s, 2H) . ES HRMS m/z 381.0230 (M+H C 19 HI 3 BrN 2 0 2 requires 381.0233). Example 146 2- [4- (benzyloxy) -3-bromo-2-oxopyridin1 (2H) -yl] benzonitrile Preparation of 2-[4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]benzonitrile 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6- methylpyridin-2(iH)-one(100 mg, 0.36 mmol) was suspended in dimethylsulfoxide (5 mL), cesium carbonate (375 mg, 1.15 mmol) was added and the reaction was shaken for 5 minutes. 4Fluorobenzonitrile (52 mg, 0.43 mmol) was then added and the reaction was heated to 80"C with stirring. Reaction was monitored by LC/MS, and after 4h was heated to 100"C and stirred for 16 hours. The reaction mixture was partitioned between water and ethyl acetate and extracted with ethyl acetate (5 x 50 mL) . The organic extracts were combined, washed with brine, dried over Na S0 4 , and filtered. The filtrate was concentrated to an oil, and purified by chromatography (silica gel, hexane/ethyl acetate) to yield white solid (18 rag, 13%). IH NMR (400 MHz, CDCI 3 ) 6 7.81 (dd, = 1.2, 8.4 Hz, IH), 7.73 (dt, J = 1.2, 8.0 Hz, IH), 7.57 (dt, J = 0.8, 8.0 Hz, IH), 7.50-7.36 (m, 6H), 7.27 (d, J = 8.0 Hz, IH), 6.28 (d, J = 8.0 Hz, IH) ; 5.31 (s, 2H). ES HRMS m/z 381.0249 (M+H C 19 HI 3 BrN 2 0 2 requires 381.0233).Example 147 (4-{ [4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]methyl}phenyl)acetic acid 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(IH)- one(0.5g, 1.78 mmol) was dissolved in N,N-dimethylformamide (5 mL). 4-(Bromomethyl)phenylacetic acid (0.5 g, 2.14 mmol) was added followed by K 2 CO (0.3 g, 2.14 mmol). The reaction was heated to 80"C and shaken for 16 hours, then heated to 100"C and shaken for 16 hours more. The reaction mixture was partitioned between water and ethyl acetate and extracted with ethyl acetate (2 x 50 mL). The aqueous layer was acidified (pH 2) with IN HCI and extracted with ethyl acetate (3 x ml) . The organic extracts were combined, washed with brine, dried over Na 2 SO 4 , and filtered. The filtrate was concentrated to an oil, and purified by chromatography (silica gel, hexane/ethyl acetate) followed by reversed phase chromatography (C 18 , 0.1% aqueous trifluoroacetic acid /acetonitrile) to yield a white solid (25 rag, 3%). IH NMR (400 MHz, CDCI 3 ) 6 7.40-7.38 (m, 3H), 7.25-7.20 (m, 7H), 6.05 (d, J = 8.0 Hz, IH), 5.21 (s, 2H) ; 5.13, (s, 2H) ; 3.62, (s, 2H) . ES HRMS m/z 428.0510 (M+H C 21 HIaBrNO requires 428.0492). Example 148 (4-[(4-(benzyloxy)-3-bromo-2-( [4-(carboxymethyl)benzyl]oxy}- llambdaS-pyridin-l-yl methyl]phenyl}acetic acid Preparation of {4- [(4- (benzyloxy)-3-bromo-2-{ [4- (carboxymethyl) benzyl ] oxy } - 11 ambda s -pyridin1 - yl)methyl]phenyl}acetic acid. The desired product was isolated by reversed phase chromatography (C 18 , 0.1% aqueous trifluoroacetic acid/acetonitrile) using the preparation of Example 147 yielding a white solid (53 rag, 5%). IH NMR (400 MHz, CDCI 3 ) 6 7.40-7.38 (m, 3H), 7.27-7.24 (m, 6H), 7.20 (d, J = 7.6 Hz, IH), 7.14 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.4 Hz, IH), 6.06 (d, J = 7.6 Hz, IH), 5.21 (s, 2H) ; 5.11 (s, 2H) ; 5.11 (s, 2H) ; 3.63 (s, 2H); 3.58 (s, 2H) . ES HRMS m/z 576.1009(M+H C 30 H 28 BrN0 6 requires 576. 1016) . Example 149 2-([3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]methyl}benzonitrile O N Preparation of 2-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}benzonitrile. 3-bromo-4- (2,4-difluorophenoxy)-6-methylpyridin-2(iH)-one (50 mg, 0.15 mmol) was dissolved in tetrahydrofuran (2 mL). e-Bromo-otolunitrile (44 mg, 0.23 mmol) was added followed by sodium hydride (7.2 mg, 0.18 mmol, 60% in mineral oil) and sodium iodide (56 mg, 0.38 mmol) . The reaction was heated to 50"C and stirred for 16 hours. The reaction was filtered through Celite and the filtrate was concentrated to an oil that was oanti.tioned h tween_wa ter and. eth¥ acetate and extracted with ethyl acetate (4 x i0 mL). The organic extracts were combined, washed with brine, dried over MgSO and filtered. The filtrate was concentrated to an oil, and purified by chromatography (silica gel, hexane/ethyl acetate) to yield a white solid (25 rag, 37%). IH NMR (400 MHz, CDCI 3 ) 6 7.68 (dd, J = 8.0, 1.2 Hz, IH); 7.58 (app q, J = 8.8 Hz, IH); 7.52 (dr, J = 8.0 & 1.2 Hz, IH), 7.38 (t, J = 7.6 Hz, IH); 7.08 (d, J = 8.8 Hz, IH) , 7.00-6.93 (m, IH) ; 6.89-6.84 (m, IH) ; 6.05 (s, IH), 5.57 (s, 2H), 5.22 (s, 2H) ; 2.28, (s, 3H). ES HRMS m/z 445.0335 (M+H C 21 HIsBrF 2 N 2 0 2 requires 445.0358) . Example 150 3- ( [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl] methyl}benzonitrile O The title compound was prepared by a procedure essentially as described in Example 149 using 3-bromo-4-(2,4difluorophenoxy)-6-methylpyridin-2(iH)-one (i g, 3.0 mmol) as starting material. IH NMR (CDCI 400 MHz) 6 7.61-7.55 (m, 2H) ; 7.45-7.41 (m, 3H) ; 6.98-6.94 (m, 114) ; 6.89-6.84 (m, IH) ; 6.03 (s, IH), 5.36 (s, 2H), 5.22 (s, 2H); 2.30, (s, 3H) . ES HRMS m/z 445.0349 (M+H C 21 HIsBrF 2 N 2 0 2 requires 445.0358) Example 151 4- ( [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2-oxopyridin1 (2H) -yl] methyl }benzonitrile O The title compound was prepared by a procedure essentially as described in Example 149 using 3-bromo-4-(2,4difluorophenoxy) -6-methylpyridin-2 (iH)-one (i g, 3.0 mmol) as starting material. ZH NMR (400 MHz, CDCI 3 ) 6 7.61 (d, J = 8.4 Hz, 2H) ; 7.62-7.56 (m, IH) ; 7.27 (d, J = 8.8 Hz, 2H) ; 6.95 (app t, J = 8.4 Hz, IH), 6.88-6.83 (m, IH) ; 6.03 (s, IH), 5.39 (s, 2H), 5.21 (s, 2H) ; 2.28 (s, 3H). ES HRMS m/z 445.0359 (M+H CnHzsBrF 2 N 2 0 2 requires 445.0358). Example 152 4-{[3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]methyl}benzamide F O H 2 N EXAMPLE 151 (50 mg, 0.ii mmol) was added to a suspension or potassium fluoride (40% on alumina) in t-butyl alcohol. The reaction was heated to 90"C and stirred for 20 hours. Alumina was removed by filtration and washed with dichloromethane and water. The resulting filtrate was separated and the aqueous layer was extracted with dichloromethane (2 x 20 mL). The organic extracts were combined, dried over Na 2 SO 4 and filtered. The filtrate was concentrated to an oil which was purified by chromatography (silica gel, hexane/ethyl acetate) to yield a white solid, yielding the product (13 rag, 25%). IH NMR (400 MHz, CDCI ) 7.75 (app d, J = 8.4 Hz, 2H), 7.58 (app q, J = 8.4 Hz, IH); 7.24 (d, J = 8.4 Hz, 2H) ; 6.98-6.94 (m, IH), 6.89-6.83 (m, IH) 6.01 (s, IH) ; 5.40 (s, 2H), 5.21 (s, 2H) ; 2.28 (s, 3H) . ES HRMS m/z 463.0486 (M+H C 21 HIvBrF N 2 0 3 requires 463.0463). Example 153 Methyl 4-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl ] methyl } benzoate O O O EXAMPLE 151 (50 mg, 0.ii mmol) was suspended in methanol and cooled to 0"C. HCI (g) was bubbled through the mixture until saturated (-30 minutes). Reaction was sealed, warmed to ambient temperature, and stirred for 2 hours. HCI and methanol were removed in vacuo, yielding an oil, that was purified by chromatography (silica gel, hexane/ethyl acetate) to yield a white solid (19 rag, 36%). IH NMR (400 MHz, CDCI 3 ) 7.97 (app d, J = 8.4 Hz, 2H), 7.58 (app q, J = 8.0 Hz, IH); 7.22 (d, J = 8.4 Hz, 2H); 6.95 (app dr, J = 1.5, 9.6 Hz, IH), 6.89-6.83 (m, IH), 6.00 (s, IH); 5.41 (s, 2H), 5.21 (s, 2H); 3.90, (s, 3H); 2.27 (s, 3H). ES HRMS m/z 478.0461 (M+H C 22 HIsBrNO 4 requires 478.0460) . Example 154 Methyl 3-{ [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}benzoate O O The title compound was prepared by a procedure essentially as described in Example 149 using the title compound of Example 150 as starting material.iH NMR (400 MHz, CDCI 3 ) 6 7.95-7.92 (m, IH) ; 7.84 (bs, IH) ; 7.58 (app q, J = 8.0 Hz, IH) ; 7.397.37 (m, 2H) ; 6.95 (app dt, J = 1.6, 8.4 Hz, IH), 6.88-6.83 (m, IH) , 6.00 (s, IH) ; 5.40 (s, 2H) , 5.21 (s, 2H) ; 3.90, s, 3H); 2.30 (s, 3H). ES HRMS m/z 478.0449 (M+H C 22 HIBBrNO 4 requires 478.0460). Example 155 3- ( [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl] methyl}benzamide The title compound was prepared by a procedure essentially as described in Example 152 using the title compound of Example 150 as starting material. IH NMR (400 MHz, CDCI 3 ) 6 7.68-7.66 (m, 2H), 7.57 (app q, J = 8.4 Hz, IH) ; 7.42-7.34 (m, 2H) 6.98-6.92 (m, IH), 6.89-6.83 (m, IH) 6.01 (s, IH) ; 5.39 s, 2H), 5.21 (s, 2H); 2.28 (s, 3H) . ES HRMS m/z 463.0461 M+H C 21 HIvBrF 2 N 2 0 3 requires 463.0463) . Example 156 2-{ [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]methyl}benzamide O The title compound was prepared by a procedure essentially as described in Example 152 using the title compound of Example 149 as starting material. IH NMR (400 MHz, CDCI 3 ) 6 7.68-7.66 (m, 2H) , 7.57 (app q, J = 8.4 Hz, IH) ; 7.42-7.34 (m, 2H) ; 6.98-6.92 (m, IH), 6.89-6.83 (m, IH) 6.01 (s, IH) ; 5.39 (s, 2H), 5.21 (s, 2H); 2.28 (s, 3H). ES HRMS m/z 463.0461 (M+H C 21 HIvBrF 2 N 2 0 3 requires 463.0463). IH NMR (400 MHz, CDCI 3 ) 6 5.24 (s, 2H) ; 2.43 (s, 3H) . ESHRMS m/z 463.0467 (M+H CnHITBrF 2 N 2 0 3 requires 463.0463) . Example 157 I- [2-(aminomethyl)benzyl]-3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methylpyridin-2(iH)-one F O EXAMPLE 149 (50 rag, 0.II retool) was dissolved in tetrahydrofuran (2 mL) under N 2 . Borane-methyl sulfide complex (0.Ii mL, 0.22 mmol, 2M in tetrahydrofuran) was added. The reaction was then heated to 70"C and shaken overnight. After cooling to ambient temperature, all the solvent was distilled under vacuum. The resulting residue was partitioned between ethyl acetate and 0.2 N NaOH, and extracted with ethyl acetate (3 x 20 mL). The organic extracts were combined, washed with brine, and dried over Na 2 SO 4 , and filtered. The filtrate was concentrated to an oil, and purified by chromatography (silica gel, hexane/ethyl acetate) to yield a white solid, to give product (19 rag, 39%). IH krMR (400 MHz, CDCI 3 ) 6 7.56-7.55 (m, 2H) ; 7.32-7.25 (m, 2H) ; 7.00-6.94 (m, IH) , 6.88-6.84 (m, IH) ; 6.81-6.79 (m, IH) ; 6.11 (s, IH) ; 5.44 (s, 2H), 5.17 (s, 2H) ; 4.59 (s, 2H) ; 2.18 (s, 3H) . ESHRMS m/z 449.0692 (M+H C 21 HIgBrF 2 N 2 0 2 requires 449.0671) . Example 158 3-bromo-l-[3-(bromomethyl)benzyl]-4-[(2,4-difluorobenzyl)oxy]- 6-methylpyridin-2(IH)-one Br O Preparation of 3-bromo-l-[3-(bromomethyl)benzyl]-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(IH)-one. 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin2(IH)-one (2 g, 6.06 mmol) was suspended in 1,4-dioxane (250 mL) . -Dibromo-m-xylene (8 g, 30.3 mmol) was added followed by sodium hydride (0.3 g, 7.5 mmol, 60% in mineral oil). The reaction was heated to 60"C and stirred for 16 hours. The reaction was filtered through Celite® and the filtrate was concentrated to an oil that was partitioned between water and dichloromethane and extracted with dichloromethane (4 x 250 mL). The organic extracts were combined, washed with brine, dried over Na 2 S0 4 , and filtered. The filtrate was concentrated to an oil, and purified by chromatography (silica gel, hexane/ethyl acetate) to yield a white solid (l.2g, 38%). IH NMR (400 MHz, CDCI 3 ) 6 7.57 (app q, J = 7.6 Hz, IH) ; 7.28-7.25 (m, 2H) ; 7.17 (s, IH) ; 7.08 (m, iH) ; 6.94 (app dt, J = 1.2, 9.6 Hz, IH), 6.87-6.82 (m, IH) ; 5.99 (s, IH) , 5.34 (s, 2H), 5.20 (s, 2H) ; 4.43 (s, 2H) ; 2.29 (s, 3H). ES HRMS m/z 511.9672 (M+H C 21 HIvBr 2 F 2 NO 2 requires Example 159 3-bromo-l-[4-(bromomethyl)benzyl]-4-[(2,4-difluorobenzyl)oxy]- 6-methylpyridin-2(iH)-one The title compound was prepared by a procedure essentially as described in Example 158. IH NMR (400 MHz, CDCI 3 ) 6 7.68-7.66 (m, 2H), 7.57 (app q, J = 8.4 Hz, IH) ; 7.42-7.34 (m, 2H) ; 6.98-6.92 (m, IH), 6.89-6.83 (m, !H) 6.01 (s, IH); 5.39 (s, 2H), 5.21 (s, 2H); 2.28 (s, 3H). ES HRMS m/z 463.0461 (M+H C 21 HI BrF 2 N 2 0 3 requires 463.0463).iH NMR (400 MHz, CDCI 3 ) 6 7.56 (app q, J = 7.6 Hz, IH); 7.32(d, J = 8.0 Hz, 2H); 7.14 (d, J = 8.0 Hz, 2H) ; 6.94 (app t, J = 8.4 Hz, IH) , 6.87-6.82 (m, IH) ; 5.98 (s, IH), 5.33 (s, 2H), 5.19 (s, 2H) ; 4.44 (s, 2H) ; 2.29 (s, 3H). ES HRMS m/z 511.9683 (M+H C 21 HITBr 2 F 2 NO 2 requires 511. 9667). Example 160 l-[4-(aminomethyl)benzyl]-3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methylpyridin-2(iH)-one O Example 159 (200 mg, 0.39 mmol) was suspended in methanol (3 mL) and cooled to -78 "C. Ammonia (g) was bubbled through the mixture for 30 minutes. The reaction vessel was sealed, allowed to reach ambient temperature, and stirred for 4 hours. The solvent and ammonia were removed from the reaction in vacuo with stirring and the resulting oil was triturated with ether to yield a solid (174 rag, 99%). IH NMR (400 MHz, CD 3 OD) 6 7.61 (q, J = 7.6 Hz, IH); 7.40 (d, J = 8.0 Hz, 2H); 7.20 (d, J = 8.0 Hz, 2H) ; 7.03 (app t, J = 8.8 Hz, 2H), 6.51 (s, IH), 5.43 (s, 2H), 5.29 (s, 2H) ; 4.07 (s, 2H) ; 2.36 (s, 3H) . ES HRMS m/z 449.0673 (CnHIgBrF 2 N 2 0 2 requires 449.0671). Examples 161-168 The compounds of Examples 161-168 are prepared essentially according to the procedures set forth above for Examples 158160 or by using the compound of Example 158: O Example No. R Ex. 161-NH 2 Ex. 162 morphol in4 -yl Ex. 163 dimethylamino Ex. 164 i sopropyl amino Ex. 165 piperidinl-yl Ex. 166( 2 - hydroxye thyl ) ami no Ex. 167 bis ( 2 - hydroxyet hyl ) amino Ex. 168 piperazinl-yl M+H ESHRMS MF Requires m/z C 21 HIgBrF 2 N 2 0 2 449.0671 449.0694 C 2 sH 2 sBrF 2 N 2 0 3 519.1089 519.1132 C 23 H 23 BrF 2 N 2 0 2 477.0984 477.0991 C 4 H 2 sBrF 2 N 2 0 2 491.1140 491.1121 C 2 H 27 BrF 2 N 2 0 2 517.1297 517.1341 C 23 H 2 BrF 2 N=O 493.0933 493 .0961 C 2 sH 27 BrF 2 N 2 0 4 537.1195 537.1171 C 2 sH 2 BrF 2 N 3 0 2 518.1249 518. 1280 NMR characterization of compounds of Examples 161-168 Ex. No. NMR Data 2.0, Hz, IH), (m, IH); (s, IH), 5.34 (s, 2H), 5.19 (s, 2H); 3.73 (s, 2H); 2.28 (s, 3H); 2.82 (app heptet, J = 6.0 Hz, IH), 1.07 (d, J = 6.0 Hz, 6H) Ex. 165 IH NMR (400 MHz, CD 3 OD) 6 7.61 (app q, J = 8.0 Hz, Ill); 7.27 (app t, J = 8.0 Hz, IH) ; 7.20 (app d, J = 7.6 Hz, IH) ; 7.08 (bs, IH) ; 7.01 (app t, J = 8.0 Hz, 2H) ; 6.48 (s, IH) , 5.41 (s, 2H) , 5.28 (s, 2H); 3.44 (s, 2H) ; 2.35 (s, 3H) ; 2.40-2.30 (m, 4H) ; 1.571.53 (m, 4H) ; 1.48-1.38 (m, 2H) Ex. 166*H NMR (400 MHz, CDCI 3 ) 7.51 (app q, J = 8.0 Hz, IH} ; 7.22-7.14 (m, 3H); 7.09 (bs, IH) ; 6.98 (app d, J = 7.2 Hz, IH) ; 6.89 (app dt, J = 1.6, 8.0 }{z, IH) ; 6.81-6.76 (m, IH) ; 5.92 (s, IH) , 5.28 (s, 2H), 5.14 (s, 2H) ; 3.73 (s, 2H) ; 3.59 (app t, J = 4.8 Hz, 2H) ; 2.73 (app t, J = 4.8 Hz, 2H) ; 2.24 (s 3H) Ex. 167 IH NMR (400 MHz, CDHOD) 6 7.61 (app q, J = 8.0 Hz, IH) ; 7.46 (app d, J = 8.8 Hz, 2H) ; 7.31 (bs, IH) ; 7.27 (app t, J = 8.0 Hz, IH) ; 7.03 (app t, J = 8.8 Hz, 2H); 6.54 (s, IH), 5.44 (s, 2H), 5.30 (s, 2H) ; 4.47 (s, 2H) ; 3.90-3.84 (m, 4H) ; 3.40-3.25 (m, 4H) ; 2.40 (s, 3H) Ex. 168 IH NMR [400 MHz, CODED) 6 7.62 lapp q, J = 8.0 Hz, IH) ; 7.53-7.46 (m, 2H); 7.36 (bs, IH) ; 7.30 (app d, J = 7.6 Hz, IH); 7.05-7.01 (m, 2H) ; 6.55 (s, IH) , 5.44 (s, 2H) , 5.30 (s, 2H) ; 4.47 (s, 2H) ; 3.58-3.53 (m, 8H) ; 2.42 (s, 3H) Example 169 3-{ [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]methyl}benzoic acid O O Preparation of 3-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}benzoic acid. EXAMPLE 154 (150 mg, 0.31 mmol) was dissolved in tetrahydrofuran (5 mL). Potassium trimethylsilanolate (80 mg, 0.62 mmol) was added and the reaction was stirred at ambient temperature for 4 hours. The reaction mixture was concentrated to an oil that was partitioned between water and ethyl acetate and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over Na SO 4 , and filtered. The filtrate was concentrated to an oil and purified by reversed phase chromatography (C 1 s, 0.1% aqueous trifluoroacetic acid/acetonitrile) to yield the product (64 mg, 44%) IH NMR (400 MHz, CD 3 OD) 6 7.92 (app d, J = 8.0 Hz, IH) ; 7.78 (s, IH) 7.62 (app q, J = 8.0 Hz, IH) ; 7.44 (t, J = 7.6 Hz, IH) ; 7.36 (app d, J = 8.0 Hz, IH) ; 7.02 (app t, J = 7.6 Hz, 2H) ; 6.51 (s, IH), 5.48 (s, 2H), 5.30 (s, 2H); 2.37 (s, 3H). ES HRMS m/z 464.0328 (C 21 HI BrF 2 NO 4 requires 464.0304). Examples 170-174 The compounds of Examples 170-174 are prepared using the compound of Example 159 or 161: R O Example M+H ESHRMS No. R MF Requires m/z :Ex. 170 -C(O)CH 3 C 2 HnBrF 2 N 2 0 3 491.0776 491.0772 Ex. 171 -C (O)'OCH 3 C 3 H 21 BrF 2 N 2 0 4 507. 0726 507. 0731 Ex. 172 ~SO CH 3 C 22 H 21 BrF 2 N 2 0 4 S 527 . 0446 527. 0430 Ex. 173 -C (O) CH 2 OH C 23 H 21 BrF 2 N 2 0 4 507. 0726 507. 0712 Ex. 174 I C(O)NH 2 C 22 H 20 BrF 2 N 3 0 3 492.0729492.0751 I N-MR characterization of compounds of Examples 170-.174 Ex. No. NMR Data Ex. 170 H NMR (400 MHz, CD 3 OD) 6 7.61 (app q, J = 8.0 Hz, IH) ; 7.28 (app t, J = 8.0, IH) , 7.18 (app d, J = 8.0 Hz, IH) , 7.05-7.00 4H) ; 6.49 (s, IH) , 5.41 (s, 2H) , 5.29 (s, 2H) ; 2.37 (s, 3H) 1.94 (s, 3H) Ex. 171 IH NMR (400 MHz, CDCI 3 } 5 7.57 (app q, J = 7.6 Hz, 2H); 7.25 (app t, J = 8.0, IH) , 7.17 (app d, J = 8.0 Hz, IH) , 7.06-7.02 2}{); 6.97-6.91 (m, IH) ; 6.87-6.82 (m, IH), 5.98 (s, IH), 5.33 (s, 2H) , 5.19 (s, 2H) ; 4.30 (d, J = 6.0 Hz, 2H) ; 3.67 (s, 3H) 2.28 (s, 3H) Ex. 172 H NMR (400 MHz, CD 3 CN) 6 7.58 (app q, J = 7.6 Hz, IH) ; 7.31 (app t, J = 8.0, IH), 7.24 (app d, J = 8.0 Hz, IH), 7.11 (s, IH) 7.05-7.00 (m, 3H) ; 6.32 (s, IH), 6.06 (bs, IH) , 5.31 (s, 2H) 5.23 (s, 2H) ; 4.17 (d, J = 6.4 Hz, 2H) ; 2.78 (s, 3H); 2.28 3H) Ex. 173 IH NMR (400 MHz, CDCI 3 ) 6 7.55 (app q, J = 8.0 Hz, IH) ; 7.23 (app t, J = 7.6, IH), 7.15 (app d, J = 7.2 Hz, IH), 7.05-7.00 3}{); 6.94 (app dt, J = 1.2, 8.8 Hz, IH); 6.88-6.81 (m, IH) ; 6.03 (s, IH) , 5.27 (s, 2H) , 5.19 (s, 2H) ; 4.39 (d, J = 6.4 Hz, 2H) 4.05 (s, 2H) , 2.31 (s, 3H) Ex. 174 IH NMR (400 MHz, CD 3 OD) 6 7.62 (app q, J = 8.0 Hz, IH) ; 7.28 (app t, J = 8.0, IH) , 7.19 (app d, J = 8.0 Hz, IH), 7.05-6.96 4H) ; 6.49 (s, IH), 5.41 (s, 2H), 5.29 (s, 2H) ; 4.25 (s, 2H) 2.35 (s, 3H) Examples 175-185 The compounds of Examples 175-175 are prepared using the compounds of Examples 159 or 160: Example NO. R Bx. 175-CH 2 NHCH(CH 3) 2 M+H ESHRMS MF Requires m/z C 24 H 2 sBrF 2 N 2 0 2 491.1140 491.1143 !EX. 176 norpholin-4-ylmethyl C 2 sH 2 sBrF 2 N 2 0] 519.1089 1519.1062 EX. 177-CH 2 N(CH 3) 2 C 23 H 23 BrF 2 N 2 0 2 477.0984 1 477.0931 Ex. 178 piperidin-l-ylmethyl C 26 H 2 vBrF 2 N 2 0 2 517.1297 517.1258 hydroxyet hyl ) amino] m ehtyl 180CH 2 NHCH 2 CHHOH 181)ipera zin1 - zlmethyl 182CH 2 NHC (O) OCHa 183CH 2 NHC (O) CH 3 184:- CH 2 NHSO 2 CH 3 185CH 2 NHC (O) NH 2 CusH 26 BrF 2 N 3 0 2 C 23 HnBrF 2 N 2 0 4 C 23 HnBrF 2 N 2 0 3 C 22 H 21 BrF 2 NzO 4 S C 22 H 20 BrFHN 3 0 3 characterization of compounds of Examples NO. NMR Data 175 IH NMR (400 MHz, CDCIa) 6 7.56 (q, J = 8.0 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H) , 6.94 IH), 6.88-6.80 (m, IH) ; 5.97 (s, IH), 5.31 2H) ; 3.74 (s, 2H); 2.82 (app heptet, J = 6.0 3H) 1.09 (d, J 6.4 Hz, 6H) Example 186 4-(4-([3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}benzoyl)piperazine-l-carboxamide O MANNHEIM 2 o o 3-bromo-4-(2,4-difluorophenoxy)-6-methyl-l-[4-(piperazinl-ylcarbonyl)benzyl]pyridin-2(IH)-one (300 mg, 0.54 mmol) was dissolved in N,N-dimethylacetamide (5 mL). Trimethylsilyl isocyanate (0.15 mL, 1.08 mmol) was added followed by N,Ndiisopropylethylamine (0.23 mL, 1.3 mmol) and the reaction was stirred for 1 hour at ambient temperature. The reaction was then diluted with tetrahydrofuran (40 mL) and polyamine resin (1.3 g, 2.81 mmol/g) and methylisocyanate functionalized polystyrene (I g, 1.38 mmol/g) were added. The mixture was shaken for 6 hours, filtered, and the resulting filtrate was concentrated to a white solid (279 mg, 90%). IH NMR (400 MHz, 2.37 (s, 3H). ES HRMS m/z 575.1104 (C 26 H 2 sBrF 2 N 4 0 4 requires 575.1100). Example 187 N-(4-{[3-bromo-4-[ 2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}benzyl)-2-methoxyacetamide FF 0 H polymer bound carbodiimide resin (2.3 g, 1.18 meq/g, 2.7 mmol) was suspended in N,N-dimethylformamide. Acetoxyacetic acid (120 mg, 1.33 mmo!) was added, followed by 1hydroxybenzotriazole (1M in N,N-dimethylforrnamide, 0.165 mL) and N,N-diisopropylethylamine (0.3 mb, 2.0 mmol). The reaction was shaken for 1 hour when EXAMPLE 159 (300 mg, 0.67 mmol) was added. The reaction was shaken for 16 hours and then diluted with tetrahydrofuran. Polyamine resin (i g, 2.81 mmol/g) and methylisocyanate functionalized polystyrene (2 g, 1.38 mmol/g) were added and the mixture was shaken for 72 hours, filtered and the resulting filtrate concentrated. Trituration with water followed by trituration with ether yielded a white solid (125 mg, 36%). IH NMR (400 MHz, CDCI ) 6 7.56 (app q, J = 8.0 Hz, IH); 7.21 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 6.94 (app t, J = 8.8 Hz, IH), 6.88-6.81 (m, IH) ; 5.97(s, IH), 5.33 (s, 2H), 5.19 (s, 2H) ; 4.43 (d, J 6.0 Hz, 2H) ; 3.92 (s, 2H) ; 3.39 (s, 3H) ; 2.29 (s, 3H) . ES HRMS m/z 521.0882 (C 24 H 22 BrF 2 N 2 0 4 requires 521.0882) . Examples 188-193 By following the general method for the preparation of Example 187 and substituting the appropriate carboxylic acid for acetoxyacetic acid, the compounds of Examples 188-193 are prepared. These compounds were triturated with water and again with ether and purified by chromatography (silica gel, hexane/ethyl acetate) as appropriate to yield off-white solids. Example 191 was prepared from its N-t-butoxycarbonyl protected intermediate. Deprotection was accomplished with 4N HCI in dioxane to afford the title compound as its hydrochloride salt (86 mg, 24%). Deprotection of the methyl ester from Ex. 188 was accomplished with K 2 CO 3 in methanol/water to yield Ex. 192 as a white solid. The yields and analytical data are shown below. ICompound% M+H ESHRMS No. R Yield MF Requires m/z Ex. 188 CH 2 OCOCH 3 4 9 C 25 H 23 BrF 2 N=Os 549.0831 549.084 Ex. 189 C (CH 3 ) 2 OH 13 C 2 sH 2 sBrF 2 N 2 0 4 535.1039 535.103£ Ex. 190 C ( - CH 2 CH 2 - ) OH 33 C 2 sH 23 BrF 2 N 2 0 4 535.0865 535.0876 Ex. 191 C H 2 1% 2 24 C 23 H 22 BrFHN 3 0 533.0882 533.0899 Ex. 192 CH 2 OH 25 C 23 H 21 BrFHN 2 0 4 507.0726 507.0730 Ex. 193 ZH2NHCOCH 3 1 81 U 25 H 24 BrF 2 N 3 OI 1548.0991 548.1000 Example 194 l-{4-[(4-acetylpiperazin-l-yl)carbonyl]benzyl}-3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one O 0 0 3-bromo-4- (2,4-difluorophenoxy) -6-methyl-l- [4-(piperazinl-ylcarbonyl)benzyl]pyridin-2(iH)-one (200 rag, 0.36 mmol) was dissolved in N,N-dimethylformamide (5 mL) . N,NDiisopropylethylamine (0.25 mL, 1.44 mmol) was added followed by acetic anhydride (0.i0 mL, 1.06 mmol) . The reaction was stirred for 2 hours at ambient temperature, and concentrated to an oil that was triturated in ether and again in water to yield an off-white solid (131 rag, 63%) IH NMR (400 MHz, CD 3 OD) 6 7.62 (app q, J = 8.0 Hz, IH) ; 7.42 (d, J = 8.0 Hz, 2H) , 7.23 (d, J = 8.0 Hz, 2H), 7.62-7.02 m, IH); 7.02 (app t, J = 8.0 Hz, 1 H) ; 6.52 (s, IH) , 5.46 (s 2H), 5.30 (s, 2H) ; 3.80-3.65 (m, 8H) ; 2.37 (s, 3H) ; 2.11 (s, 3H) . ES HRMS m/z 574.1150 (C 27 H 2 BrF 2 N 3 0 4 requires 574.1148 Example 195 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- (4- { [4- (methyl sul fonyl ) piperaz in1 -yl ] carbonyl } benzyl ) pyridin - 2 (IH) - 3-bromo-4- (2,4-difluorophenoxy) -6-methyl-I- [4- (piperazin-lylcarbonyl)benzyl]pyridin-2(!H)-one (300 rag, 0.54 retool) was dissolved in N,N-dimethylformamide (5 mL) . 4~Methylmorphoiine (0.23 mL, 2.2 mmol) was added followed by methanesulfonyl chloride (0.i0 mL, 1.33 mmol) and the l-eaction was stirred for 2 h. The reaction was then diluted with tetrahydrofuran (40 mL) and polyamine resin (1.3 g, 2.81 retool/g) and methylisocyanate functionalized polystyrene (I g, 1.38 mmol/g) were added. The mixture was shaken for 16 hours, filtered, and the resulting filtrate concentrated to an oil that was triturated with water. The resulting white solid was collected, washed with ether and dried (172 mg, 52%). IH NMR (400 MHz, CDCI 3 ) 6 7.57 (app q, J = 8.2 Hz, IH) ; 7.34 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.02 (app dr, J = 1.2, 8.8 Hz, IH), 6.88-6.82 (m, IH); 6.02 (s, IH), 5.37 (s, 2H), 5.21 (s, 2H) ; 3.80-3.20 (m, 8H) ; 2.79 (s, 3H) ; 2.30 (s, 3H) . ES HRMS m/z 610.0851 (C 26 H 26 BrF 2 N 3 OsS requires 610.0817). Example 196 Methyl-4-[4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]benzoate. O O Step i. Preparation of 4- [4- (benzyloxy)-2-oxopyridin-l(2H)- yl] benzonitrile. 4-benzyloxy-2(IH)-pyridone (12.00 g, 59.63 mmol) was dissolved in dimethyl sulfoxide (I00 mL) . Potassium carbonate (10.99 g, 79.50 mmol) was added, followed by 4-fluorobenzonitrile (4.81 g, 39.75 mmol). The reaction was stirred at I00 °C for 18 hours. After cooling to room temperature the reaction was diluted with H 2 0 (150 mL) and the solids were collected by filtration washing with diethyl ether. Chromatography (silica gel, hexanes/ethyl acetate) provided an off-white solid (7.78 g, 65%). IH NMR (300 MHz, CDCI 3 ) 6 7.79 (d, J = 8.3 Hz, 2H), 7.54 (d, J = 8.5 Hz, 2H), 7.44-7.41 (m, 5H), 7.22 (d, J = 13.3, IH), 6.13 (dd, J = 2.6, 7.7 Hz, IH), 6.06 (d, J = 2.6 Hz, IH), 5.07 (s, 2H) . Step 2. Preparation of 4-[4-(benzyloxy)-3-bromo-2-oxopyridinl(2H)-yl]benzonitrile 4-[4-(benzyloxy)-2-oxopyridin-l(2H)-yl]benzonitrile (Step I) (2.76 g, 9.13 mmol) was suspended in acetonitrile (50 mL) and cooled in an ice-bath. N-bromosuccinimide (1.71 g, 9.54 mmol) was added. Once the addition was complete the cooling bath was removed. After stirring for 45 minutes the reaction was diluted with acetonitrile and solids were collected by filtration to give a white solid (3.13 g, 90% ZH NMR (300 MHz, DMSO-d 6 ) 6 8.00 (d, J = 8.5 Hz, 2H), 7.84 (d, J = 7.9 Hz, IH), 7.66 (d, J = 8.5, 2H), 7.50-7.37 (m, 5H), 6.63 (d, J = 7.9 Hz, IH) , 5.41 (s, 2H) . Step 3. Preparation of methyl-4-[4-(benzyl)oxy-3-bromo-2oxopyridin-l(2H)-yl]benzoate. 4-[4-(benzyloxy)-3-bromo-2oxopyridin-l(2H)-yl]benzonitrile (Step 2) (1.50 g, 3.93 mmol) suspended in methanol (50 mL) was cooled in an ice-bath. HCI (g) was then bubbled through the mixture for 5 minutes. The reaction was then stirred at room temperature overnight, at which time the reaction mixture was concentrated. The residue was suspended in 6N HCI (60 mL) and heated at reflux for 1.5 hours. After cooling to room temperature the solids were collected by filtration. Chromatography (silica gel, hexanes/ethyl acetate) provided an off-white shiny solid (0.540 g, 61%). IH NMR (400 MHz, DMSO-d ) 6 8.04 (d, J = 8.5 Hz, 2H), 7.81 (d, J = 7.8 Hz, IH), 7.55 (d, J = 8.6 Hz, 2H), 7.47-7.39 (m, 5H), 6.57 (d, J = 7.9 Hz, IH), 5.38 (s, 2H), 3.86 (s, 3H). ES-HRMS m/z 416.0355 (M+H caldc for C 20 HI 6 BrNO 4 requires 414.0341). Example 197 4-[4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)-yl]benzoic acid. Preparation of 4-[4-(benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]benzoic acid. EXAMPLE 196 (0.460 g, i.ii mmol) was dissolved in tetrahydrofuran (5.0 mL) . Potassium trimethylsilanolate (0.285 g, 2.22 mmol) was added. The reaction was stirred at room temperature for 3 hours at which time H 2 0 (i0 mL) was added. The aqueous reaction mixture was acidified (pH-3) with IN HCI. The tetrahydrofuran was evaporated, additional H 2 0 (50 mL) was added and the aqueous layer was extracted with ethyl acetate (2 x 50 mL) . The combined organic layers were washed with brine (50 mL), dried over Na 2 SO 4 , filtered and evaporated to provide a rust colored solid (0.444 g, 100%). IH NMR (400 MHz, DMSO-d 6 ) 68.02 (d, J = 8.6 Hz, 2H), 7.80 (d, J = 7.8 Hz, IH), 7.55 (d, J = 8.6 Hz, 2H), 7.50-7.34 (m, 5H), 6.57 (d, J = 7.9 Hz, IH), 5.38 (s, 2H). ES-HRMS m/z 400.0191 (M+H calcd for C 19 HI 4 BrN0 4 requires 400.0184). Example 198 4- [4- (benzyloxy) -3-bromo-2-oxopyridin1 (2H) -yl ] benzamide. Preparation of 4- [4- (benzyloxy)-3-bromo-2-oxopyridin-l(2H)- yl]benzamide. STEP 2, EXAMPLE 196 (0.238 g, 0.624 mmol) was suspended in tert-butyl alcohol (3.0 mL). KF on 40 wt % AI 2 0 (0.453 g, 3.12 mmol) was added. The reaction mixture was heated at reflux for 5 days. Additional KF on 40 wt % A1 2 0 3 (0.453 g, 3.12 mmol) was added and heating was continued at reflux overnight. After cooling to room temperature chloroform and methanol were added and the solids were collected by filtration. Chromatography (reverse-phase, acetonitrile/H 2 0) provided a tan solid (0.073 g, 30%). H NMR (400 MHz, DMSO-d ) 68.07 (s, IH), 7.95 (d, J = 8.6 Hz, 2H), 7.79 (d, J = 7.8 Hz, IH), 7.47-7.34 (m, 7H), 6.56 (d, J = 7.9 Hz, IH), 5.38 (s, 2H) . ES-HRMS m/z 399.0372 (M+H calcd for C 19 HIsBrN 2 0 3 requires 399. 0344) . Example 199 l-[4-(aminomethyl)phenyl]-4-(benzyloxy)-3-bromopyridin-2(iH)- one. HCI Preparation of l-[4-(aminomethyl)phenyl]-4-(benzyloxy)-3bromopyridin-2(iH)-one. STEP 2, EXAMPLE 196 (1.25 g, 3.28 mmol) was dissolved in tetrahydrofuran (15 mL). Boranedimethylsulfide (3.44 mL, 6.89 mmol, 2.0 M in tetrahydrofuran) was added and the mixture heated at reflux. After 14.5 hours the solvent was evaporated. 0.5M NaOH (50 mL) was added followed by ethyl acetate. The aqueous layer was neutralized with IN HCI. Methanol saturated with HCI was added and the mixture was heated at reflux for 5 hours. After cooling to room temperature, diethyl ether was added and the solids were collected by filtration. The solids were treated with 4N HCI in dixoane (5 mL) and methanol (i mL) at room temperature for 1 hour, at which time diethyl ether was added and the solids were collected by filtration to give a tan solid (0.920 g, HRMS m/z 385.0555 (M+H calcd for C 19 HI BrN 2 0 2 requires 385.0552). Example 200 Methyl-4-[3-chloro-4-[(2,4-diflurobenzyl)oxy]-2-oxypyridinl(2H)-yl]benzoate. F\ O O Step I. Preparation of 4- [4- (benzyloxy)-2-oxopyridin-l(2H)- yl] benzonitrile. O CN 4-benzyloxy-2(IH)-pyridone (50.0 g, 248.47 mmol) was dissolved in dimethyl sulfoxide (300 mL). Potassium carbonate (68.68 g, 496.94 mmol) was added, followed by 4-fluorobenzonitrile (31.60 g, 260.89 mmol). The reaction was stirred at i00 °C for hours. After cooling to room temperature the reaction was diluted with H 2 0 (600 mL) and the solids were collected by filtration washing with diethyl ether. The solids were then washed with hot methanol to provide a tan solid (55.6 g, 74%). Step 2. Preparation of I- [4-nitrilephenyl]-4-hydroxy-2(iH)- pyridinone. O 4-[4-(benzyloxy)-2-oxopyridin-l(2H)-yl]benzonitrile (Step I) (20.0 g, 66.15 mmol) was dissolved in methanol (300 mL). Ammonium formate (8.34 g, 132.3 mmol) was added followed by Pd/C (6.62 g). The resulting mixture was heated at reflux for minutes at which time the reaction began to exotherm. The reaction was allowed to cool to room temperature at which time it was filtered through a pad of Celite® washing with methanol. The filtrate was evaporated to provide a pale yellow solid (16.2 g, >100%). IH NMR (300 MHz, CDCI 3 ) 68.46 (s, IH), 7,95 (d, J = 8.5 Hz, 2H), 7.62 (d, J = 8.5 Hz, 2H) , 7.47 (d, J = 7.7 Hz, IH), 5.98 (dd, J = 2.6, 7.7 Hz, IH), 5.54 (d, J = 2.4 Hz, IH) . Step 3. Preparation of 4-[4-[(2,4-difluorobenzyloxy)]-2oxopyridin-l(2H)-yl]benzonitrile. l-[4-Nitrilephenyl]-4-hydroxy-2(iH)-pyridinone (Step 2) (16.2 g) was dissolved in N,N-dimethylformamide (i00 mL). Potassium carbonate (10.06 g, 72.77 mmol) was added followed by -bromo2,4-difluorotoluene (8.91 mL, 69.46 mmol). The resulting mixture was heated to 65°C for 1 hour. Additional -bromo-2,4difluorotoluene (4.25 mL, 33.08 mmol) was added. The resulting mixture was heated to 65°C for 5 hours. Additional -bromo-2,4-difluorotoluene (2.12 mL, 16.54 mmol) was added. After stirring at 65°C overnight the reaction was allowed to cool to room temperature. H 2 0 (300 mL) was added and the solid was collected by filtration. A portion (8.0 g) of the solids were washed with hot methanol to give a pale yellow solid (6.22 g, 78%). H NMR (300 MHz, CDCI 3 ) 68.00 (d, J = 8.5 Hz, 2H), 7.72-7.64 (m, 2H), 7.66 (d, J = 8.5 Hz, 2H), 7.40-7.32 (m, IH) , 7.22-7.16 (m, IH), 6.17-6.11 (m, 2H), 5.17 (s, 2H) . Step 4. Preparation of methyl-4-[4-[(2,4-difluorobenzyl)oxy]- 2-oxopyridin-l(2H)-yl]benzoate. O O O 4-[4-[(2,4-difluorobenzyloxy)]-2-oxopyridin-l(2H)- yl]benzonitrile (Step 3) (2.00 g, 5.91 mmol) suspended in methanol (20 mL) and H 2 0 (5 mL) was cooled in an ice-bath. HCI (g) was bubbled through the mixture until most of the solids dissolved. The resulting mixture was then heated at. reflux or 3. ho.ur The reaction was the rec o±ed i an-ice-bath and HCI was bubbled through the mixture for 5 minutes. The mixture was heated at reflux for 2 hours and then the methanol was evaporated. Additional H 2 0 (50 mL) was added and the aqueous reaction mixture was extracted with ethyl acetate (50 mL) and tetrahydrofuran (50 mL). The combined organic layers were washed with brine (50 mL), dried over Na 2 S0 4 , filtered and evaporated. Chromatography (silica gel, hexanes/ethyl acetate with 10% methanol) gave an off-white solid (0.630 g, 29%). IH NMR (300 MHz, DMF-d 6 ) 68.15 (d, J = 8.5 Hz, 2H), 7.80 (app q, J = 7.9 Hz, IH), 7.74-7.67 (m, IH), 7.68 (d, J = 8.5 Hz, 2H), 7.42-7.34 (app dt, J = 2.4, 9.0 Hz, IH) , 7.28-7.22 (m, IH), 6.20 (dd, J = 2.6, 7.6 Hz, IH), 6.15 (d, J = 2.4 Hz, IH), 5.28 (s, 2H) , 3.98 (s, 3H) . Step 5. Preparation of methyl-4- [3-chloro-4- [ (2,4- diflurobenzyl) oxy] -2-oxypyridin-i (2H) -yl] benzoate. Methyi-4- [4- [(2,4-difluorobenzyl)oxy] -2-oxopyridin-1 (2H) -yl] benzoate (Step 4) (0.520 g, 1.40 mmol) was suspended in acetonitrile (I0.0 mL). N-chlorosuccinimide (0.196 g, 1.47 mmol) was added followed by several drops of dichloroacetic acid. The resulting mixture was heated at reflux overnight. After cooling to room temperature additional acetonitrile was added and the precipitate was collected by filtration to give an off-white solid (0.331 g, 58%). IH NMR (300 MHz, DMF-d ) 68.34 (d, J = 8.5 Hz, 2H), 8.12 (d, J = 7.9 Hz, IH), 8.04-7.96 (m, IH) , 7.88 (d, J = 8.5 Hz, 2H) , 7.59-7.53 (m, IH), 7.527.41 (m, IH), 7.05 (d, J = 7.9 Hz, IH), 5.70 (s, 2H), 4.15 (s, 3H). ES-HRMS m/z 406.0644 (M+H calcd for C 20 HI 4 CIF 2 NO 4 requires 406. 0652) . Example 201 (hydroxymethyl)phenyl]-6-methylpyridin-2(iH)-one. O Step I. Preparation of 4-Hydroxy-l-[3- (hydroxymet hyl ) phenyl ] 6 - met hylpyridi n2 ( IH ) - one. O 4-hydroxy-6-methyl-2-pyrone (i0.0 g, 79.3 mmol) and 3aminobenzyl alcohol (9.77g, 79.3 mmol) were combined in H 2 0 (I00 mL) and heat at reflux. After 48 hours at reflux the reaction mixture was concentrated. The residue was treated with methanol and the precipitate was collected by filtration to give a pale yellow solid (3.04 g, 17%). IH NMR (300 MHz, DMSO-d 6) d 10.6 (br s, IH) , 7.46-7.35 (m, 2H) , 7.09-7.03 (m, 2H), 5.88 (d, J = 1.6 Hz, IH), 5.55 (d, J = 2.6 Hz, IH), 4.54 (d, J = 4.2 Hz, 2H), 1.83 (s, 3H) . Step 2. Preparation of l-[3-(hydroxymethyl)phenyl]-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one. 4 -Hydroxy1 - [3 - (hydroxymethyl) phenyl ] 6 -methylpyridin2 (IH) -one (Step i) (0.674 g, 2.91 mmol) was suspended in acetone (i0 mL) . Cesium carbonate (1.04 g, 3.21 mmol) was added followed by -bromo-2,4-difluorotoluene (0.392 mL, 3.06 mmol) . After stirring at room temperature for 2 days the reaction was concentrated. The residue was portioned between H 2 0 (30 mL) and ethyl acetate (30 mL). The aqueous layer was further extracted with ethyl acetate (30 mL). The combined organic layers were washed with brine (30 mL), dried over Na 2 S0 4 , filtered and concentrated. Chromatography (on silica, hexanes/ethyl acetate with 10% methanol) provided a white solid (0.531 g, 51%). IH NMR (300 MHz, CDCI 3 ) 6 7.51-7.39 (m, 3H), 7.82 (s, IH), 7.16 (d, J = 26.8 Hz, IH), 7.08-6.86 (m, 2H) , 6.00 (d, J = 2.6 Hz, IH) , 5.92 (d, J = 2.6 Hz, IH), 5.05 (s, 2H), 4.68 (s, 2H), 1.93 (s, 3H). ES-HRMS m/z 358.1256 (M+H calcd for C 20 HI F 2 NO requires 358.1249). Step 3. Preparation of 3-bromo-4-[(2,4-diflurorbenzyl)oxy]-i- [3- (hydroxymethyl) phenyl] -6-methylpyridin-2 (1H) -one i- [3- (hydroxymethyl) phenyl ] - 4 - [ ( 2, 4 -di f luorobenzyl ) oxy] - 6 - methylpyridin-2(iH)-one (Step 2) (0.460 g, 1.29 mmol) was suspended in acetonitrile (5.0 mL) and cooled in an ice-bath. N-bromosuccinimide (0.241 g, 1.35 mmol) was added. Once the addition was complete the cooling bath was removed. After stirring for 1.5 hours the reaction was diluted with acetonitrile and solids were collected by filtration to give a white solid (0.385 g, 68%). IH NMR (300 MHz, DMSO-d 6 ) d 7.70 (app q, J = 7.9 Hz, IH) , 7.49-7.32 (m, 3H) , 7.24-7.10 (m, 3H) , 6.66 (s, IH), 5.35 (s, 2H), 4.56 (d, J = 5.6 Hz, 2H), 1.95 (s, 3H) . ES-HRMS m/z 436.0384 (M+H calcd for C 20 HI 6 BrF 2 NO 3 requires 436.0354) . Example 202 Methyl-4-[3-bromo-4-[(difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]benzoate. O O Step I. Preparation of Methyl 4-(4-hydroxy-6-methyl-2oxypyridin1 (2H) -yl) benzoate. O 4-hydroxy-6-methyl-2-pyrone (21.00 g, 166.70 mmol) and methylaminobenzoate (25.20 g, 166.70 mmol) were combined 1,2-dichlorobenzene (50 mL) and rapidly heated to 160 °C. After 15 minutes at 160 °C the reaction was allowed to cool room temperature. The reaction was diluted with dichloromethane (50 mL) and extracted with saturated Na 2 C0 x i00 mL). The combined aqueous layers were acidified (pH-2) with concentrated HCI. The precipitate was collected by filtration and washed with diethyl ether to give a yellow/orange solid (10.9 g, 25%). IH NMR (300 MHz, DMSO-d Step 2. Preparation of Methyl-4- [4- [(difluorobenzyl)oxy]-6methyl -2-oxopyridin1 (2H) -yl] benzoate. Methyl 4-(4-hydroxy-6-methyi-2-oxypyridin-l(2H)-yl)benzoate (Step I) (10.90 g, 42.04 mmol) was dissolved in N,Ndimethylformamide (i00 mL) . Potassium carbonate (6.97 g, 50.45 mmol) was added, followed by 2,4-difluorobenzyl bromide (5.66 mL, 44.14 mmol) . The reaction was stirred at room temperature for 3 days then diluted with H 2 0 (I00 mL). The reaction mixture was extracted into ethyl acetate and tetrahydrofuran (2 x i00 mL). The precipitate was collected by filtration and the organic filtrate was washed with brine (50 mL), dried over Na 2 S0 4 , filtered and evaporated. The resulting solid was combined with the precipitate to provide a pale pink solid (6.77 g, 42%). IH NMR (300 MHz, DMSO-d 6 ) 68.01 (d, J = 8.3 Hz, 2H), 7.67 (q, J = 7.9 Hz, IH), 7.43 (d, J = 8.3 Hz, 2H), 7.35 (m, IH), 7.18 (app dt, J = 1.6, 8.5 Hz, IH), 6.08 (d, J = 1.8 Hz, IH), 5.98 (d, J = 2.4 Hz, IH), 5.14 (s, 2H), 3.91 (s, 3H), 1.87 (s, 3H). Step 3. Preparation of methyl-4-[3-bromo-4- [(difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]benzoate. Methyl-4- [4- [(difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]benzoate (Step 2) (6.74 g, 17.49 mmol) suspended in acetonitrile (I00 mL) was cooled in an ice-bath. Nbromosuccinimide (3.27 g, 18.36 mmol) was added. After 1 hour the ice-bath was removed and after an additional 30 minutes the reaction was diluted with acetonitrile (20 mL). The precipitate was collected by filtration to provide the title compound as an off-white solid (6.94 g, 85%). IH NMR (300 MHz, CDCI 3 ) 68.20 (d, J = 8.7 Hz, 2H), 7.61 (q, J = 7.9 Hz, IH), 7.30 (d, J = 8.7 Hz, 2H), 7.02-6.96 (m, IH), 6.90 (app dt, J = 2.4, 9.5 Hz, IH), 6.14 (s, IH), 5.28 (s, 2H), 3.98 (s, 3H), 2.00 (s, 3H) . ES-HRMS m/z 464.0304 (M+H calcd for CnHI 6 BrF 2 N0 4 requires 464.0301). Example 203 4-[3-bromo-4-[(difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]benzoic acid. 0 .OH EXAMPLE 202 (7.43 g, 16.00 mmol) was dissolved in tetrahydrofuran (40 mL) . Potassium trimethylsilanolate (4.10 g, 32.00 mmol) was added and the reaction mixture was stirred at room temperature for 22 hours. The tetrahydrofuran was evaporated and H 2 0 (50 mL) was added. The aqueous reaction mixture was acidified with IN HCI and the precipitate was collected by filtration. The solids were washed with boiling 6.72 (s, IH), 5.37 (s, 2H), 1.97 (s, 3H) . ES-HRMS m/z 450.0154 (M+H calcd for C 20 HI BrF N0 4 requires 450.0147). Example 204 4-(Benzyloxy)-l-(3-fluorobenzyl)-3-(trifluoromethyl)pyridin2(iH)-one. O The starting material (0.250 g, 0.591 mmol) was dissolved in 1-methyl-2-pyrrolidinone (5.0 mL). Trifluoroacetic acid, sodium salt (0.322 g, 2.36 mmol) was added, followed by copper(I)iodide (0.225 g, 1.18 mmol). The resulting mixture was heated to 180°C for 5 hours and then allowed to cool to room temperature. The reaction was diluted with H 2 0 (50 mL) and brine (50 mL), then extracted into ethyl acetate (2 x mL). The combined organic layers were washed with brine (50 mL), dried over Na 2 SO 4 , filtered and evaporated. Chromatography (reverse-phase, acet 0 nitrile/H 2 0) provided an off-white solid (0.050 g, 22%). IH NMR (400 MHz, CDCI ) 6 7.40-7.27 (m, 8H), 7.06 (d, J = 7.7 Hz, IH), 6.97 (d, J = 9.0 Hz, IH), 6.07 (d, J = 7.7 Hz, IH), 5.20 (s, 2H), 5.06 (s, 2H) ES-HRMS m/z 378.1097 (M+H calcd for C 0 HIsF 4 N0 2 requires 378.1112). Example 205 4- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridinl(2H)-yl]methyl}benzoic acid O EXAMPLE 153 (50.0 g, 104.54 mmol) was dissolved in methanol (500 mL) and dioxane (I00 mL). IN NaOH (130 mL, 130 mmol was added. The resulting mixture was heated to 50 °C for 5.5 hours. The reaction was partially concentrated and the heterogenous mixture was acidified (pH 2) with IN HCI. The precipitate was collected by filtration to afford a white solid (49.2 g, >I00 %). IH NMR (300 MHz, DMSO-d 6 ) 6 7.94 (d, J = 8.3 Hz, 2H), 7.70 (app q, J = 7.9 Hz, IH), 7.35 (dt, J = 2.2, 9.9 Hz, IH) , 7.18 (app d, J = 8.3 Hz, 2H) , 7.17-7.12 (m, IH), 6.64 (s, IH), 5.41 (s, 2H), 5.33 (s, 2H) , 2.32 (s, 3H) . ES-HRMS m/z 464.0327 (M+H calcd for C 21 HI 6 BrF NO 4 requires 464.0304). Example 206 3-Bromo-4-[(2,4-diflurobenzyl)oxy]-l-[4- (hydroxymethyl)benzyl]-6-methylpyridin-2(iH)-one. Example 205 (40.0 g, 86.16 mmol) suspended in tetrahydrofuran (300 mL) was cooled in an ice-bath. Borane dimethylsulfide (129.2 mL, 258.48 mmol, 2.0 M in tetrahydrofuran) was slowly added. The resulting mixture was slowly allowed to warm to room temperature overnight. The mixture was recooled in an ice-bath and quenched by the addition of small pieces of ice. After the evolution of gas ceased additional ice-water was added. The flask was fitted with a distillation apparatus and the dimethylsulfide was removed. After the reaction was cooled to room temperature, H O (300 mL), ethyl acetate (200 mL) and tetrahydrofuran (300 mL) were added. The precipitate that formed was collected by filtration and the filtrate was placed in a separatory funnel. The aqueous layer was further extracted with ethyl acetate (300 mL) . The combined organic layers were washed with brine (300 mL). The organic phase was dried over Na 2 S0 4 and evaporated which was combined with the precipitate to yield an off-white solid (37.8 g, 97%). IH NMR (400 MHz, CDCI 3 ) 6 7.47 (app q, J = 7.7 Hz, IH), 7.23 (d, J = 7.9 Hz, 2H), 7.05 (d, J = 7.9 Hz, 2H), 6.86 (app dt, J = 2.3, 8.6 Hz, IH) , 6.79 (app dr, J = 2.4, 8.4 Hz, IH) , 6.00 (s, 1H) , 5.28 (s, 2H), 5.16 (s, 2H), 4.57 (s, 2H), 2.25 (s, 3H) . ESHRMS m/z 450.0512 (M+H calcd for C 21 HIsBrF 2 NO 3 requires 450.0511) . Example 207 methylethyl)benzyl]-6-methylpyridin-2(IH)-one. F\ Preparation of 3-bromo-4-[(2,4-diflurobenzyl)oxy]-l-[4-(lhydroxy-l-methylethyl)benzyl]-6-methylpyridin-2(IH)-one. EXAMPLE 153 (2.00 g, 4.18 mmol) suspended in tetrahydrofuran (20 mL) was cooled in the dry ice/acetone bath. Methyl magnesium bromide (4.32 mL, 12.96 mmol, 3.0 M in diethyl ether) was slowly added. The reaction was slowly allowed to warm to room temperature overnight. The reaction was then cooled in an ice bath and quenched by the addition of saturated NH 4 CI (50 mL). H 2 0 was added and the reaction was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na 2 S0 4 , filerted and evaporated. The residue was subjected to chromatography (silica gel, hexanes/ethyl acetate with 10% methanol) to provide an off-white foam. The foam was dissolved in acetonitrile and cooled in an ice bath. N-bromosuccinimide (0.057 g, 0.320 mmol) was added. Once the addition was complete the cooling bath was removed. After 2.5 hours at room temperature the reaction was concentrated. Purification by chromatography (silica gel, hexanes/ethyl acetate with 10% methanol) provided a white foam. IH NMR (400 MHz, CDCI ) 6 (s, 3H), 1.52 (s, 6H) . ES-HRMS m/z 478.0811(M+H C 23 H 22 BrF 2 NO requires 478.0824). Example 208 3-bromo-4-[(2,4-diflurobenzyl)oxy]- 6-methyl-l-{4- [(methylamino)methyl]benzyl}pyridin-2(iH)-one. O HN Step I. Preparation of 4-{ [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}benzaldehyde. O O EXAMPLE 206 (1.30 g, 2.89 mmol) was suspended in acetonitrile (i0 mL) and cooled in an ice-bath, l-hydroxy-l,3-dihydro-3,3bis(trifluoromethyl)-l,2-benziodoxole 1-oxide (0.580 g, 1.44 mmol) was added and the reaction mixture was stirred at room temperature overnight. Diethyl ether was added and the solid was collected by filtration to give a white solid (1.14 g, Step 2. 3-bromo-4- [(2,4-diflurobenzyl)oxy]- 6-methyl-l-{4- [ (methylamino) methyl] benzyl }pyridin-2 (IH) -one. 4-{ [3-Bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2~oxopyridin-i (2H) - yl]methyl}benzaldehyde (Step i) (1.53 g, 3.41 mmol) of step was dissolved in N,N-dimethylformamie (5.0 mL) . Methylamine (3.41 mL, 6.83 mmol, 2.0 M in tetrahydrofuran) was added followed by NaHB(OAc) 3 (2.17 g, 10.23 retool) in N,Ndimethylformamide (8.0 mL) and acetic acid (2.0 mL). The reaction was stirred at room temperature overnight at which time IN NaOH (50 mL) was added and then extracted with ethyl acetate (2 x 50 mL). The organic layers were washed with brine (25 mL), dried over Na 2 S04 and evaporated. Chromatography ( on silica, ethyl acetate with 5% methanolic ammonia/hexanes) afforded a tan solid (0.810 g, 53%). H NMR (400 MHz, CDCI 3 ) 6 7.55 (app q, J = 7.8 Hz, IH), 7.22 (d, J = 8.I Hz, 2H), 7.11 (d, J = 8.1 Hz, 2H), 6.92 (app dt, J = 2.4, 8.3 Hz, IH), 6.90-6.80 (m, IH), 5.95 (s, IH), 5.32 (s, 2H), 5.17 (s, 2H), 3.68 (s, 2H), 2.40 (s, 3H), 2.27 (s, 3H) . ESHRMS m/z 463.0838 (M+H calcd for C 22 H 21 BrF 2 N 2 0 4 requires 463.0827) . Example 209 4-[(2,4-diflurobenzyl)oxy]-l-(4-methoxybenzyl)-6methylpyridin-2-(iH)-one. Step i. Preparation of i-(4-methoxybenzyl)-4-hydroxy-6methylpyridin-2 (IH) -one. O O m 4~Hydroxy-6-methyl-2-pyrone (4.60 g, 36.45 mmol) and 4methoxybenzylamine (5.00 g, 36.45 retool) in H O (I00 mL) were heated to reflux. After 15 hours at reflux the reaction was allowed to cool to room temperature. The precipitate was collected by filtration washing with H 2 0 to give a pale yellow solid (8.00 g, 89 %). IH NMR (400 MHz, DMSO-d 6 ) 6 7.2 (d, J 8.7 Hz, 2H) , 6.85 (d, J = 8.7 Hz, 2H), 5.74 (d, J = 2.0 Hz, IH), 5.56 (d, J = 2.5 Hz, IH), 5.08 (s, 2H), 3.68 (s, 3H), 2.14 (s, 3H) . Step 2. Preparation of 4-[(2,4-diflurobenzyl)oxy]-l-(4methoxybenzyl)-6-methylpyridin-2(IH)-one. 1-(4methoxybenzyl)-4-hydroxy-6-methylpyridin-2(iH)-one (Step i) (7.97 g, 32.49 mmol) was dissolved in N,N-dimethylformamide (60 mL) . Potassium carbonate (4.94 g, 35.74 mmol) was added, followed by ~bromo-2,4-difluorotoluene (4.38 mL, 34.11 mmol) The reaction was stirred at room temperature for 20 hours at wn±ch time the mixture was filtered through a pad. of Celite® washing with acetonitrile and the filtrate was evaporated. The residue was dissolved in H 2 0 (150 mL) and extracted into ethyl acetate (2 x I00 mL). The organic phase was washed brine (i00 mL), dried over Na 2 S0 4 , filtered and evaporated. Chromatography (on silica, hexanes/ethyl acetate with 10% methanol) yielded an off-white solid (3.64 g, 30%). IH NMR (300 MHz CDCI 3 ) 6 7.42 (app q, J = 7.7 Hz, IH), 7.13 (d, J 8.5 Hz, 2H) , 6.96-6.84 (m 2H) , 6.85 (app d, J = 8.7 Hz, 2H) 6.01 (d, J = 2.6 Hz, IH) , 5.82 (d, J = 2.8 Hz, IH), 5.23 (s, 2H), 5.02 (s, 2H), 3.79 (s, 3H), 2.25 (s, 3H) . ES-HRMS m/z 372.1412 (M+H C 21 HIgF 2 NO 3 requires 372.1417) . Example 210 3-bromo-4-[(2,4-diflurobenzyl)oxy]-l-(4-methoxybenzyl)-6methylpyridin-2(iH)-one O O-- Preparation of 3-bromo-4-[(2,4-diflurobenzyl)oxy]-l-(4- methoxybenzyl)-6-methylpyridin-2(IH)-one. EXAMPLE 209 (0.200 g, 0.538 mmol) suspended in acetonitrile (3 mL) was cooled an ice-bath. N-bromosuccinimide (0.I01 g, 0.565 mmol) was added. Once the addition was complete the cooling bath was removed. After 1 hour the reaction was concentrated. purification by chromatography (silica gel, hexanes/ethyl acetate) provided a white solid (0.240 g, 99%). IH NMR (300 5.21 (s, 2H), 3.79 (s, 3H), 2.34 (s, 3H) . ES-HRMS m/z 450.0491 (M+H C 21 HIsBrF 2 NO requires 450.0511). Example 211 3-bromo-4-[(2,4-diflurobenzyl)oxy]-l-(4-hydroxybenzyl)-6methylpyridin-2(iH)-one F O OH Preparation of 3-bromo-4-[(2,4-diflurobenzyl)oxy]-l-(4hydroxybenzyl)-6-methylpyridin-2(IH)-one. EXAMPLE 210 (0.235 g, 0.522 mmol) was suspended in acetonitrile (3 mL). Cerric ammonium nitrate (1.14 g, 2.09 mmol) dissolved in H 2 0 (i mL) was added. The reaction was stirred at room temperature for 1 hour and then diluted with dichloromethane (25 mL) . The reaction was then washed with H 2 0 (I0 mL). The aqueous phase was back extracted with dichloromethane (20 mL). The combined organic layers were dried over Na 2 S0 4 , filtered and evaporated. The residue was washed with hot ethyl acetate to give an offwhite solid (0.134 g, 59%). IH NMR (300 MHz, DMSO-dG) 67.75 (app q, J = 7.9 Hz, IH), 7.65 (s, IH), 7.45-7.36 (m, IH), 7.36 (d, J = 10.1Hz, 2H), 7.27-7.20 (m, IH), 6.49 (d, J = i0.i Hz, 2H), 5.60 (s, 2H), 5.07 (s, 2H), 2.63 (s, 3H). ES-HRMS m/z 436.0187 (M+H C 20 HI 6 BrF 2 NO requires 436.0354). Example 212 methylpiperidinl-yl) carbonyl] benzyl } -6-methylpyridin-2 (!H) - one. O O Step i. Preparation of 4-hydroxy-4-methylpiperidine hydrochloride. HN OH HOf tert-Butyl-4-oxo-l-piperidine (i0.0 g, 50.19 mmol) dissolved in diethyl ether (i00 mL) was cooled in an ice-bath. Methyl magnesium bromide (18.40 mL, 55.21 mmol, 3.0 M in diethyl ether) was added. After slowly warming to room temperature the reaction was recooled in an ice-bath and quenched by the addition of saturated NH 4 CI (75 mL). Additional H 2 0 was added and the organic layer was removed. The aqueous layer was further extracted with diethyl ether (50 mL). The combined organic layers were washed with brine, dried over Na 2 SO 4 , filtered and concentrated. Chromatography ( silica gel, hexanes/ethyl acetate) provided a clear oil. The resulting oil was dissolved in diethyl ether (i0 mL) and treated with 4N HCl/dioxane (32.61 mL, 130.43 mmol). After stirring at room temperature for 1 hour the reaction mixture was concentrated Step 2. Preparation of 3-bromo-4-[(2,4-difluorobenzyl)oxy]- l{4-[(4-hydroxy-4-methylpiperidin-l-yl)carbonyl]benzyl}-6methylpyridin-2(iH)-one. THE ACID (0.300 g, 0.646 mmol) was suspended in dichloromethane (6.0 mL) . l-hydroxybenzotriazole (0.044 g, 0.323 mmol) was added followed by 3-(1cyclohexylcarbodiimide)propyl-functionalized silica gel (2.02 g, 1.29 mmol, loading = 0.64 mmol/g), 3-(l-morpholine)propyl functionalized silica gel (1.84 g, 5.29 mmol, loading = 0.7 mmol/g) and dichloromethane (2 mL). After stirring at room temperature for 15 minutes, 4-hydroxy-4-methylpiperidine hydrochloride (0.147 g, 0.969 mmol) was added. The resulting mixture was stirred at room temperature overnight, at which time dimethylamine-3-functionalized silica gel (1.7 g, 2.58 mmol, loading = 1.5 mmol/g) was added followed by isocyanate3-functionalized silica gel (1.3 g, 1.62 mmol, loading = 1.22 mmol/g). The resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was then filtered and concentrated. Chromatography (silica gel, hexanes/ethyl acetate with 10% methanol) provided a white foam (0.200 g, 55%). IH NMR (300 MHz, CDCI 3 ) 6 7.58 (app q, J = 7.7 Hz 0 IH), 7.33 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 8.1 Hz, 2H), 6.96 (app t, J = 8.3 Hz, IH), 6.87 (app dr, J = 2.0, 9.5 Hz, IH), 6.06 (s, IH), 5.38 (s, 2H), 5.22 (s, 2H), 4.27 (br m, IH), 3.41 (br m, 3H), 2.30 (s, 3H), 2.06 (s, IH), 1.60 (br m, 4H), 1.28 (s, 3H). ES-HRMS m/z 561.1173 (M+H C 2 vH 2 vBrF 2 N 2 O 4 requires 565.1195) . Example 213 oxypyridin-l(2H)-yl]methyl}-N-(2-hydroxy-2methylpropyl)benzamide. O OH The title compound was by a procedure essentially as in Example 212 using l-amino-2-methyl-2-propanol hydrochloride as starting material. IH NMR (400 MHz, CDCI 3 ) 6 7.70 (d, J = 8.3 Hz, 2H), 7.53 (app q, J = 7.8 Hz, !H), 7.33 (t, J = 5.8 Hz, IH), 7.06 (d, J = 8.3 Hz, 2H), 6.95-6.90 (m, IH), 6.86-6.81 (m, IH), 6.04 (s, IH), 5.30 (s, 2H), 5.19 (s, 2H), 3.40 (d, J = 5.9 Hz, 2H), 2.98 (br s, IH), 2.24 (s, 3H), 1.21 (s, 6H). ES-HRMS m/z 535.1012 (M+H C 2 sH 2 sBrF 2 N 2 0 4 requires 535.1039). Example 214 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -I { 4- [ (4-hydroxypiperidinl-yl) carbonyl] benzyl } -6-methylpyridin-2 (IH) -one. The title compound was produced essentially as in Example 212 using 4-hydroxypiperidine as starting material. IH NMR (400 MHz, CDCI 3 ) 6 7.55 (app q, J = 7.7 Hz, IH), 7.30 (d, J = 8.2 Hz, 2H), 7.15 (d, J = 8.3 Hz, 2H), 6.94 (app dt, J = 2.4, 8.4 Hz, IH) , 6.84 (app ddd, J = 2.6, 8.9, 10.3 Hz, IH) , 6.01 (s, IH), 5.36 (s, 2H) 0 5.19 (s, 2H), 4.12-4.07 (m, IH), 3.96-3.90 (m, IH), 3.60 (br s, IH), 3.33 (br s, IH), 3.13 (br s, IH), 2.27 (s, 3H), 1.91 (br s, 3H), 1.77 (br s, IH), 1.57 (br s, IH), 1.44 (br s 0 IH) . ES-HRMS m/z 547.1006 (M+H C 26 H 2 sBrF 2 N 2 0 4 requires 547.1039) . Example 215 4- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-2-oxopyridin1 (2H) -yl] methyl } -N- (2 -hydroxyethyl) benzamide. Preparation of 4-{ [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-i(2H)-yl]methyl}-N-(2hydroxyethyl)benzamide. To a reaction vesse! (borosilicate culture tube) was added EXAMPLE 205 (0.300 g, 0.646 mmol). A stock solution of l-hydroxybenzotriazole in N,Ndimethylformamide (3 mL, 0.!i M) was added to the reaction vessel followed by approximately I.i0 g of the polymer bound carbodiimide resin (1.8 mmol/g). Additional N,Ndimethylformamide (2 mL) was then added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for 15 minutes. Ethanolamine (0.06 mL, 0.994 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this Lime the reaction was diluted with tetrahydrofuran (20 mL) and treated with approximately 2.0 g of polyamine resin (2.63 mmol/g) and approximately 2.6 g of methylisocyanate functionalized polystyrene (I.I0 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature for 3 hours. The reaction vessel was then opened and the solution phase product was separated from the insoluble quenched byproducts by filtration and collection into a vial. After partially evaporation the insoluble byproducts were rinsed further with tetrahydrofuran (2 x i0 mL) and combined with the partially reduced filtrate. The resulting filtrate was concentrated by blowing N 2 over the vial while heating (60 °C) in a reaction block (KEM-Lab Parallel Reactor) to give an off-white solid. (0.iii g, 34%) IH NMR 3.64-3.60 (m, 2H), 2.47-3.42 (m, 2H), 2.40 (s, 3H). ES-HRMS m/z 507.0742 (M+H C 23 HnBrF 2 N 2 0 4 requires 507.0726). Example 216-231 Preparation of 3-bromo-4- (2,4-difluorophenoxy)-6-methyl-l- [4- (aminocarbonyl) benzyl ] pyridin2 (IH) -one compounds ,R 1 0 R 2 By following the method of Example 215 and substituting the appropriate amine, the compounds of Examples 216-231 are prepared. The deprotection of the protected intermediates was accomplished with 4N HCI in dioxane to afford the compounds as hydrochloride salts. Compound% M+H No. R 1 R 2 Yield MF Requires 2H 2 CH 2 NHCH 2 CH 2 NHEx. 216 73 C 25 H 24 BrF 2 N 0 4 532.1042 532.102 Ex. 217[4 CH 2 CH 2 NH 2 49 C 23 H 22 BrF 2 N 3 0 3 506.0885 506.088 Ex. 218[4 CH 2 CH 2 CH 2 NH 2 31 C 24 H 24 BrF 2 N 3 0 3! 520.1042 520.104 Ex. 219 iH OH 53 C 21 HITBrF 2 N 2 0 4 479.0413 479.042 Ex. 220[4 CH 3 59 C 22 HIgBrF 2 N 2 0 4 m 477.0620 477.06C Ex. 221 ICH 3 CH 51 C 23 HnBrF 2 N 2 0 3 491.0776 91.07S Ex. 222 NCH 2 CH 2 0CH 2 CH 2 0 - 61 C 2 sH 23 BrF 2 N 2 0 4 533.0882 533.09C Ex. 223!CHmCHiOH CH 2 CHHOH 69 C 2 sH 2 sBrF 2 N 2 Os 551.0988 551.095 Ex. 224 CHaCHiCH 2 - CH 2 CHaCH 2 - 66 C 2 sHasBrFaN 2 0 3 531.1084 531 Ex. 231 CH 3 82 C 2 sH 2 sBrF 2 N 2 0 4 535. 1039 535. Example 232 4- { [3-bromo-4- [ (2,4-di fluorobenzyl) oxy] - 6-methyl-2-oxopyridin1 (2H)-yl]- N- (2-hydroxyethyl)benzamide. H O 3H O Preparation of 4-{ [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]- N-(2-hydroxyethyl)benzamide. To a reaction vessel (borosilicate culture tube) was added EXAMPLE 203 (0.300 g, 0.666 mmol). A stock solution of lhydroxybenzotriazole in N,N-dimethylformamide (3 mL, 0.ii M) was added to the reaction vessel followed by approximately 1.13 g of the polymer bound carbodiimide resin (i.8 mmol/g). Additional N,N-dimethylformamide (2 mL) was then added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for 15 minutes. Ethanolamine (0.06 mL, 0.994 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with tetrahydrofuran (20 mL) and treated with approximately 2.0 g of polyamine resin (2.63 mmol/g) and approximately 2.7 g of methylisocyanate functionalized polystyrene (I.i0 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature for 3 hours. The reaction vessel was then opened and the solutlon phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partially evaporation the insoluble byproducts were rinsed further with tetrahydrofuran (2 x I0 mL) and combined with the partially reduced filtrate. The resulting filtrate was concentrated by blowing N 2 over the vial while heating (60 °C) in a reaction block (KEM-Lab Parallel Reactor). Purification by chromatography (silica gel) provided an off-white solid (0.155 g, 47%). IH NMR (400 MHz, DMF-dG) 6 8.58 (t, J = 5.5 Hz, IH), 8.10 (d, J = 8.3 Hz, 2H), 7.79 (app q, J = 7.9 Hz, IH), 7.47 (d, J = 8.3 Hz, 2H), 7.36-7.30 (m, IH), 7.21 (app dt, J = 2.4, 8.5 Hz, IH), 6.73 (s, IH), 5.43 (s, 2H), 3.68 (app t, J = 5.9 Hz, 2H), 3.52-3.49 (m, 2H), 2.03 (s, 3H) . ES-HRMS m/z 493.0597 (M+H C 22 HIgBrF 2 N 2 0 4 requires 493.0569). Examples 233-243 Br R 1 O L N,R 2 O By following the method of Example 232 and substituting ethanolamine for the appropriate amine, the compounds of Examples 233-243 are prepared. The deprotection of the protected intermediates was accomplished with 4/ HCI in dioxane to afford the compounds as hydrochloride salts. Compound% M+H ESHRMS No. E 1 R 2 Yield MF Requires m/z Ex. 233 CH 2 CH 2 NHCH 2 CH 2 NH40.3 C 24 H 22 BrF 2 N]O 3 !518. 0885 518.086E Ex. 234 IH CH 2 CH 2 N-H 2 57.1 C 22 H 20 BrF 2 N 3 0 3 4 92. 072 9 492.074 Ex. 235 CH 2 CH 2 CH 2 NH 2 21.5 C 23 HnBrF 2 N 3 0 3 506. 0885 506.091£ Ex. 236 H OH 33.9 C 20 HIsBrF 2 N 2 0 4 465. 0256, 465.025S Ex. 237 H CH 20.7 C 21 HIvBrF 2 N 2 0 3 463.0463 463.047S Ex. 238 CH 3 CH 3 22.3 C= 2 HIgBrF 2 N 2 0 3 477. 0620 1477.0643 Ex. 239 CH 2 CH 2 0ZH 2 CH 2 0Ex. 240 CH 2 CH 2 OH H 2 CH 2 OH Ex. 241 CH 2 CH 2 CH - CH 2 CH 2 CH 284.4 C 24 H 21 BrF 2 N O 4 519. 0726!519. 072 46.6 C 24 H 23 BrF 2 N 2 0s 537. 0831 537.0854 76.51 C 2 sH 23 BrF 2 N 2 0 3 517. 0933 517.0892 Ex. 242 H CH ( CH 3 ) 2 Ex. 243 CH 2 CH 2CH 2 CH 252.6 C 2 H 21 BrF 2 N 2 0 491. 0776 491.0781 47.2 C 24 H 21 BrF 2 N 2 0 4 503. 0776 503.0791 Ex. 244 4-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]benzamide. O Preparation of 4-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]benzamide. EXAMPLE 203 (0.500 g, i. Ii mmol) was suspended in tetrahydrofuran (5.0 mL). 2Chloro-4,6-dimethoxy-l,3,5-triazine (0.234 g, 1.33 mmol) was added followed by 4-methylmorpholine (0.366 mL, 3...3.3 mmol). hours at which time NH 4 OH (2.5 mL) was added. The resulting mixture was stirred at room temperature overnight. H 2 0 (25 mL) and tetrahydrofuran (25 mL) was added. The aqueous layer was further extracted with ethyl acetate (25 mL). The combined organic layers were washed with saturated sodium carbonate solution (25 mL), IN HCI (25 mL), brine (25 mL), dried over Na 2 SO4, filtered and concentrated to provide a pale yellow solid (0.500 g, I00 %). IH N-MR (400 MHz, DMF-d 6 ) 6 8.13 (s, IH), 8.02 (d, J = 8.5 Hz, 2H), 7.70 (app q, J = 7.9 Hz, IH) 0 7.40 (d, J = 8.5 Hz, 2H), 7.41-7.34 (m, IH), 7.22 (app dt, J = 1.8, 8.5 Hz, IH), 6.71 (s, IH), 5.37 (s, 2H), 1.97 (s, 3H). ES-HRMS m/z 449.0281 (M+H C 20 HIsBrF 2 N 2 0 3 requires 449.0307). Ex. 245 4- (Benzyloxy) -3-bromo-l- [4- (morpholin-4ylcarbonyl) phenyl] pyridin-2 (IH) -one. O Preparation of 4-(Benzyloxy)-3-bromo-l-[4-(morpholin-4ylcarbonyl)phenyl]pyridin-2(iH)-one. To a reaction vessel (borosilicate culture tube) was added EXAMPLE 197 (0.i00 g, 0.250 mmol) which was dissolved in N,N-dimethylformamide (2.0 mL). l-Hydroxybenzotriazole (0.017 g, 0.125 mmol) was added to the reaction vesse! followed by approximately 0.423 g of the polymer bound carbodiimide resin (1.8 mmol/g). Additional N,N-dimethylformamide (2 mL) was then added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for 15 minutes. Morpholine (0.033 g, 0.0.375 mmol) dissolved in N,N-dimethlyformamide (0.5 mL) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with N,N-dimethylformamide (2.0 mL) and dichloromethane (4.0 mL) and treated with approximately 0.770 g of polyamine resin (2.63 mmol/g) and approximately 1.0 g of methylisocyanate functionalized polystyrene (i.i0 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature for 3 hours. The reaction vessel was then opened and the solution phase product was separated from the insoluble quenched byproducts by filtration and collection into a vial. After partially evaporation the insoluble byproducts were rinsed with dichloromethane (2 x i0 mL). The filtrate was evaporated by blowing N 2 over the vial while heating (60 °C) in a reaction block (KEM-Lab Parallel Reactor) to give an off-white solid (0.092 g, 79%). IH N-MR (400 MHz, CDCI 3 ) 6 7.50 (d, J = 8.5 Hz, 2H) , 7.48-7.33 (m, 7H), 7.27 (d, J = 7.8 Hz, IH) , 6.19 (d, J = 7.8 Hz, IH), 5.29 (s, 2H), 3.76-3.47 (br m, 8H). ES-HRMS m/z 469.0733 (M+H C 23 HnBrN 2 0 4 requires 469.0757). Ex. 246 4-(Benzyloxy)-3-bromo-l-[4-(piperazin-lylcarbonyl)phenyl]pyridin-2(IH)-one hydrochloride. Preparation of 4- (benzyloxy)-3-bromo-l- [4- (piperazin-lylcarbonyl)phenyl]pyridin-2 (IH) -one hydrochloride. By following the method of Ex. 245 and substituting N-tert-butyl carboxylate piperazine (0.070 g, 0.375 mmol) for morpholine the title compound was prepared as the N-t-butoxycarbonyl protected compound. The deprotection of the N-tbutoxycarbonyl intermediate was accomplished with 4N HCI in dioxane to afford the title compound as its hydrochloride salt (0.112 g, >100%). !H NMR (400 MHz, DMSO-d ) 6 9.55 (br s, 2H), 7.78 (d, J = 7.8 Hz, IH), 7.58 (d, J = 8.5 Hz, 2H) , 7.48-7.33 (m, 7H), 6.57 (d, J = 7.8 Hz, IH), 5.38 (s, 2H), 3.79-3.36 (br m, 4H), 3.30-3.14 (br s, 4H). ES-HRMS m/z 468.0940 (M+H C 23 H 22 BrN 3 0 requires 468.0917). Ex. 247 4- [4- (Benzyloxy) -3-bromo-2-oxopyridin-I (2H) -yl] -Nhydoxybenzamide. H O O Preparation of 4- [4- (Benzyloxy)-3-bromo-2-oxopyridin-I (2H)- yl]-N-hydoxybenzamide. By following the method of EXAMPLE 245 and subst itut ing O- (tetrahydro2H-pyranyl - 2yl ) hydroxylamine (0.044 g, 0.375 mmol) for morpho!ine the title compound was prepared as the tetrahydropyranly protected compound. The deprotection of the tetrahydropyranly intermediate was accomplished with 4N HCI in dioxane to afford the title compound (0.056 g, >71%). H NMR (400 MHz, DMSO-d ) 6 11.03 (br s,iH), 7.83 (d, J = 8.6 Hz, 2H), 7.78 (d, J = 7.8 Hz, IH), 7.48-7.35 (m, 7H), 6.55 (d, J = 7.8 Hz, IH), 5.37 (s, 2H). ES-HRMS m/z 415.0278 (M+H C 19 HIsBrN 2 0 4 requires 415.0288). Ex. 248 Methyl-4- { [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -6-methyi-2oxopyridin1 (2H) -yl ] methyl } benzoate. O Step i. Preparation of 3-chloro-4- [(2,4-difluorobenzyl)oxy]- 6-methylpridin-2 (IH) -one (5.00 g, 19.90 mmol) was suspended in 1,2-dichloroethane (I00 mL). Dichloroacetic acid (0.082 mL, 0.995 mmol) was added, followed by N-chlorosuccinimide (3.19 g, 23..88 mmol). The reaction mixture was heated at 80 °C for 15.5 hours. The 1,2dichloroethane was evaporated and the remaining solids were washed with acetonitri!e to provide a tan solid (4.97 g, 88%). Step 2. Preparation of methyl-4-{ [3-ch!oro-4-[(2,4- difluorobenzyl)oxy]-6-methy!-2-oxopyridin-l(2H)- yl]methyl}benzoate. 3-Chloro-4-[(2,4-difluorobenzyl)oxy]-6methylpridin-2(IH)-one (Step I) (4.97 g, 17.40 mmol) suspended in tetrahydrofuran (50 mL) was cooled in an ice-bath. Methyl 4-(bromomethyl)benzoate (5.98 g, 26.10 mmol) was added, followed by sodium hydride (0.835 g, 20.88 mmol, 60% dispersion in mineral oil). Once the addition was complete the cooling bath was removed in the mixture was heated to 50 °C for 19 hours. After cooling to room temperature saturated NH 4 CI (50 mL) was added. Ethyl acetate was added and the precipitate was collected by filtration. The filtrate was further extracted with ethyl acetate. The combined organic layers were washed with brine (50 mL), dried over Na 2 SO 4 , filtered and evaporated. The resulting solid was combined with the precipitate and washed with hot ethyl acetate to give an off-white solid (5.24 g, 69%). IH NMR (400 MHz, DMSO-d 6 ) 6 7.90 (d, J = 8.5 Hz, 2H), 7.63 (app q, J = 7.9 Hz, IH), 7.31 (app dt, J = 2.4, 9.9 Hz, IH), 7.21 (d, J = 8.3 Hz, 2H), 7.177.13 (m, IH), 6.60 (s, IH), 5.36 (s, 2H), 5.27 (s, 2H), 3.81 (s, 3H), 2.27 (s, 3H) . ES-HRMS m/z 434.0931 (M+H CnHIsBrF 2 NO 4 requires 434.0965) . Example 249 3- { [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2-oxopyridin1 (2H) -yl] methyl }-N-methylbenzamide To a reaction vessel borosilicate culture tube) was added EXAMPLE 169 (0.300 g, 0.646 mmol). A stock solution of lhydroxybenzotriazole in N,N-dimethylformamide (3 mL, 0.ii M) was added followed by approximately I.I0 g of the polymer bound carbodiimide resin (1.8 mmol/g). Additional N,Ndimethylformamide (2 mL) was then added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for 15 minutes. N-Methylamine (0.50 mL, 0.999 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with tetrahydrofuran (35 mL) and treated with approximately 2.0 g of polyamine resin (2.63 mmol/g) and approximately 2.6 g of methylisocyanate functionalized polystyrene (1.50 mmol/g) and the orbital shaking was continued aL 200 RPM at room temperature for 4 hours. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble filtrate was evaporated by blowing N over the vial while heating (60 °C) in a reaction block (KEM-Lab Parallel Reactor). Chromatography (C-18, acetonitrile/H O with 0.1% trif!uoroacetic acid) afforded a white solid (0.178 g, 58%). IH NMR (400 MHz, DMF-d 6 ) 6 7.65-7.53 (m, 3H), 7.37-7.28 (m, 2H) , 6.97-6.82 (m, 2H), 6.00 (s, IH), 5.36 (s, 2H), 5.19 (s, 3H) , 2.96 (t, J = 4.83 Hz, 3H), 2.29 (s, 3H) . ES-HRMS m/z 477.0635 (M+H C 22 HIgBrF 2 N 2 0 3 requires 477.0620). Preparation of Examples 250261 BrO r/ IR1 By following the method of Example 249 and replacing Nmethylamine with the appropriate amine, the compounds of Examples 250-261 are prepared. The deprotection of the protected intermediates was accomplished with 4N HCI in dioxane to afford the compounds as hydrochloride salts. Compound% M+H ES-HRMS R 1 R 2 MF No. Yield Requires m/z Example 262 l N- (3-{ [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin-l(2H)-yl]methyl}benzyl)-2-methoxyacetamide To a reaction vessel (borosilicate culture tube) was added methoxyacetic acid (0.09 g, 1.00 mmol) . A stock solution of l-hydroxybenzotriazole (3 mL, 0.16 M) and N-methylmorpholine (3 mL, 0.43 M) in N,N-dimethylformamide were added to the reaction vessel followed by approximately 0.97 g of the polymer bound carbodiimide resin (1.38 mmol/g) . Additional N,N-dimethylformamide (3 mL) was then added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature: f o 4 hours. 1-[3- (aminomethyl)benzyl]-3-bromo- - [(2,4-difluorobenzyl)oxy]-6methylpyridin-2(!H)-one (EXAMPLE 161) (0.30 g, 0.668 mmol) was then added to the reaction vessel followed by additional N,Ndimethylformamide (5.0 niL) and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with tetrahydrofuran (20 niL) and treated with approximately 2.06 g of polyamine resin (2.63 mmol/g) and approximately 2.67 g of methylisocyanate functionalized polystyrene (i.i0 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature for 4 hours. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were rinsed with tetrahydrofuran (2 x I0 mL) . The filtrate was evaporated by blowing N 2 over the vial while heating (60 °C) in a reaction block (KEM-Lab Parallel Reactor) afforded a tan solid (0.321 g, 89.4%). IH NMR (400 MHz, DMF- ) 6 8.33 (br s, IH), 7.81 (app q, J = 7.85 Hz, IH) , 7.40-7.23 (m, 5H), 7.09 (d, J = 7.25 Hz, IH), 6.68 (s, IH), 5.46 (s, 2H) , 5.42 (s, 2H), 4.45 (d, J = 6.24 Hz, 2H), 3.93 (s, 2H) , 3.39 (s, 3H) , 2.44 (s, 3H) . ESHRMS m/z 521.0891 (M+H C 24 H 23 BrF 2 N 2 0 4 requires 521.0882). Preparation of Example 263-265 By following the method of Example 262 and replacing methoxyacetic acid with the appropriate acid, the compounds of Examples 263-265 are prepared. The deprotection of the protected intermediates was accomplished with 4N HCI in dioxane to afford the compounds as hydrochloride salts. Compound% M+H ES-HRMS MF No. Yield Requires m/z Ex. 263 CH 2 NH 2 46.1 C 23 H 23 BrF 2 N 3 0 3 506.0885 506.0870 Ex. 264 DH 2 NHCOCH 3 70.4 C 2 sH 24 BrF 2 N 3 0 4 548.0991 548.1007 Ex. 265 CH 2 OCOCH 3 42.7 C 23 H 21 BrF 2 N 2 0 4 549.0831 549.0837 Example 266 H OH N- (3- { [3-bromo~4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) - yl ] me thyl } benzyl ) - 2 - hydroxy2 - methylpropanamide l-[3-(aminomethyl benzyl]-3-bromo-4- [(2,4-difluorobenzyl)oxy]- 6-methylpyridin-2 iH)-one (EXAMPLE 161) (0.300 g, 0.668 mmol), l-hydroxyisobutyrlc acid (0.215 g, 2.064 mmol), lhydroxybenzotriazole (0.112 g, 0.826 mmol), and 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.185 g, 0.963 mmol) were dissolved in N,N-dimethylacetamide (3 mL). N-methylmorpholine (0.209 g, 2.064 mmol) was added, and the reaction stil-red for 1 hour at room temperature. The reaction was diluted with H 2 0 (50 mL) and the aqueous layer extracted with ethyl acetate (3 x 25 mL). The combined organics were then washed with IN HCI (25 mL), saturated Na 2 CO (25 mL) , brine (25 mL), dried over Na 2 SO 4 , and concentrated to yield an off-white solid (0.235 g, 64%). IH NMR (400 MHz, DMF-d ) 6 8.25 (br s, IH), 7.81 (app q, J = 7.92 Hz, IH), 7.40-7.21 (m, 5H), 7.09 (d, J = 6.84 Hz, IH), 6.67 (s, IH), 5.46 (s, 2H), 5.42 (s, 2H), 4.42 (d, J = 6.24 Hz, 2H), 2.44 (s, 3H) , 1.38 (s, 6H) . ES-HRMS m/z 535.1024 (M+H C 2 sH 25 BrF 2 N 2 0 4 requires 535.1039). Example 267 OH N- (3- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin-I (2H) -yl] methyl } benzyl) - lhydroxycyc 1 opropanecarboxamide By following the method of Example 266 and substituting lhydroxy-l-cyclopropane-carboxylic acid for l-hydroxyisobutyric acid, the title compound was prepared (0.352 g, 96%). IH NMR -- 3.82 Hz, 2H) . ES-HRMS m/z 533.0861 (M+H requires 533.0882) . Example 267 O N'- (3-{ [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin1 (2H) -yl ] methy! } benzyl ) -N, N-dimethylurea Step i: Preparation of 4-nitrophenyl 3-{ [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}benzylcarbamate O H Br ! - [ 3 - (aminomethyi) benzyl] - 3 - b -Qmo_4:- [ ( : 4-di ai enzyL) was suspended in dichloromethane (15 mL) . Pyridine was added (0.43 mL, 5.34 mmol) . After stirring for I0 minutes at room temperature, a stock solution of 4-nitrophenyl chloroformate (i0.0 mL, 0.50 M) in dichloromethane was added dropwise. After stirring for 4.5 hours at room temperature, a stock solution of 4-nitrophenyl chloroformate (2.5 mL, 0.50 M) in dichloromethane was again added dropwise and stirring continued at 40 °C overnight. The reaction mixture was concentrated and subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) to afford a yellow solid (i.ii g, 66%). IH NMR (400 MHz, DMSO-d 6 ) 6 8.56 (app t, J = 6.10 Hz, IH), 8.24-8.21 (m, 2H), 7.62 (app q, J = 7.88 Hz, IH) , 7.40-7.27 (m, 7H), 6.98 (d, J = 7.52 Hz, IH), 6.54 (s, IH), 5.30 (s, 2H), 5.24 (s, 2H), 4.25 (d, J = 6.18 Hz, 2H), 2.30 (s, 3H) . ES-HRMS m/z 614.0753 (M+H C 2 eH 22 BrF 2 N 3 0 6 requires 614.0733). Step 2: Preparation of N'-(3-{[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}benzyl)-N,N-dimethylurea To a reaction vessel (borosilicate culture tube) was added 4-nitrophenyl 3-( [3bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}benzylcarbamate (from step i) (0.350 g, 0.570 mmol) dissolved in dichloromethane (6.0 mL). The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for minutes. A stock solution of N,N-dimethylamine in tetrahydorfuran (0.427 mL, 2.0 M) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. The reaction mixture was concentrated and subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) which afforded an off white solid (0.226 g, 63.3%). H NMR (400 MHz, DMF-d ) 6 7.81 (app q, J = 7.92 Hz, IH), 7.40-7.19 (m, 5H), 7.06 (d, J = 7.45 Hz, IH}, 6.88 (app t, J = 5.84 Hz, IH), 6.68 (s, IH), 5.45 (s, 2H) , 5.42 (s, IH), 4.35 (d, J = 5.84 Hz, IH), 2.92 (s, 6H) , 2.44 (s, 3H). ES-HRMS m/z 520.1065 (M+H C 24 H 24 BrF 2 N 3 0 3 requires 520.1042). Preparation of Example 268-270 O H By following the method of Example 267 and replacing N,Ndimethylamine with the appropriate amine, the compounds of Examples 268-270 are prepared. The deprotection of the protected intermediates was accomplished with 4N HCI in dioxane to afford the compounds as hydrochloride salts. Compound % M+H ES-HRMS RI R 2 MF No. Yield Requires m/z Ex. 268 CH 2 CH 2 N-CH 2 CH 2 N66.6 C 26 H 2 vBrF 2 N 4 0 3 561.1307561.1309 Ex. 269 H CH 3 27.0 C 23 Hc 2 BrF 2 N 3 0 506. 0885 506. 0898 Ex. 270 CH 2 CH 2 0-CH 2 CH 2 064.4 C 2 H 6 BrF 2 N 3 0 4 562.1148562.1137 Example 271 3 - [3-bromo-4 - [ (2,4-difluorobenzyl) oxy] - 6-methy! -2 -oxopyridinl(2H)-yl]benzoic acid. Step i: Preparation of methyl cxopyridin-l(2H)-yl)benzoate 3-(4-hydroxy-6-methyl-2Methyl 3-aminobenzoate (75.00 g, 496.13 mmol) and 4-hydroxy-6methyl-2-pyrone (62.57 g, 496.13 mmol) were suspended in 1,2dichlorobenzene (150 mL) and heated to 165 °C for 15 minutes. The reaction was cooled to room temperature and extracted with 0.54M K C0 3 (4 x 250 mL). The aqueous layers were acidified (pH 2) with 4N HCI. The precipitate was collected by filtration to afford a yellow-orange solid (20.24 g, 16%). The resulting filtrate was extracted with ethyl acetate (3 x 1 L). The organic layers were washed with brine (500 mL), dried over MgSO 4 and evaporated. The resulting solid was washed with hot H 2 0 to afford a yellow-orange solid (3.84 g, 3%). The two solids were then combined. IH N-MR (400 MHz, DMS0-d ) 6 7.98 (M+H C 14 HI 3 NO 4 requires 260.0917). Step 2: Preparation of methyl 3-[4-[(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]benzoate Methyl 3- (4-hydroxy-6-methyl-2-oxopyridin1 (2H) -yl) benzoate ( from step i) (24.00 g, 92.57 retool) and K 2 C0 3 (15.35 g, 111.08 mmol) were dissolved in N,N-dimethylformamide (220 mL) . 2,4Difluorobenzyl bromide (20.12 g, 97.20 mmol) was then added and the reaction mixture stirred for 48 hours at room temperature. The reaction mixture was diluted with H 2 0 (I L) and the precipitate collected by filtration to afford a white solid (4.08 g, 11%) . The resulting oil was purified by chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) to afford an off white solid (11.88 g, 33%). The two solids were combined. IH NMR (400 MHz, CDCI 3 ) 6 8.11 (dt, J = 1.41, 7.79 Hz, IH), 7.87 (app t, J = 1.78 Hz, IH), 7.58 (app t, J -- 7.69 Hz, IH) 7.45-7.38 (m, 2H), 6.94-6.84 (m, 2H) , 5.97 (d, J = 2.68 Hz, IH) , 5.90 (ddd, J = 0.94, 1.74, 1.74 Hz, IH), 5.97 (s, IH) , 3.90 (s, 3H) , 1.89 (s, 3H) . ESHRMS m/z 386.1179 (M+H CnHI F 2 N0 4 requires 386.1198). Step 3: Preparation of methyl 3- [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyI-2-oxopyridin-l(2H)-yl]benzoate Methyl 3- [4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridinI(2H)-yl] benzoate ( from step 2) (15.85 g, 41.130 retool) suspended in acetonitrile (165 mL) was cooled in an ice-bath. N-bromosuccinimide (7. 687 g, 43.186 mmol) was added and the ice-bath was removed. The reaction mixture was stirred for 1.5 hours at room temperature. Reaction was concentrated and subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) afforded an off white solid (17.63 g, 92%). IH NMR (400 MHz, CDCI 3 ) 6 8.17 (dt, J = 1.41, 7.85 Hz, IH) , 7.90 (t, J = 1.81 Hz, IH) , 7.67-7.41 (m, 3H) , 7.05-6.88 (m, 2H) , 6.13 (s, IH), 5.30 (s, 2H) , 3.95 (s, IH), 2.01 (s, 3H) . ES-HRMS m/z 464. 0286 (M+H C 21 HI 6 BrF 2 NO 4 requires 464.0304) . Step 4: Preparation of the title compound Methyl 3-[3bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]benzoate ( from step 3) (i0.0 g, 21.539 mmol) was dissolved in methanol (36 mL) and tetrahydrofuran (14 mL). 4N NaOH (13.5 mL, 53.847 mmol) was added. The resulting mixture was stirred for 1.5 hours at room temperature. The reaction was acidified (pH 2) with 4N HCI. The precipitate was collected by filtration to afford an off white solid (7.83 g, 81%) IH NMR (400 MHz, DMSO-d 6 ) 6 8.01 (dr, J = 1.41, 7.65 Hz, IH) , 7.76 (app t, J = 1.78 Hz, IH) , 7.76-7.15 (m, 5H), 6.66 (s, IH), 5.32 (s, 2H), 1.92 (s, 3H) . ES-HRMS m/z 450.0134 (M+H C 0 HI 4 BrF 2 NO 4 requires 450.0147). Example 272 BrO Ethyl 3- [3-bromo-4- [ (2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl] benzoate By following the method of Example 271 and substituting ethyl 3-aminobenzoate for methyl 3-aminobenzoate, the title compound was prepared (2.66 g, 79%). i}{ NMR (400 MHz, CDCI 3 ) 6 8.13 (dt, J = 1.41, 7.85 Hz, IH), 7.84 (t, J = 1.88 Hz, IH), 7.62-7.55 (m, 2H) , 7.36 (app dq, J = 1.07, 7.85 Hz, IH) , 6.96 (app dr, J = 2.55, 8.35 Hz, IH) , 6.88-6.84 (m, !H) , 6.08 (s, IH) , 5.25 (s, 2H), 4.42-4.30 (m, 2H) , 1.96 (s, 3H), 1.36 (t, J = 7.12 Hz, 3H) . ES-HRMS m/z 478.0482 (M+H C 22 HIsBrF 2 NO 4 requires 478.0460) . Example 273 F 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridinTo a reaction vessel (borosilicate culture tube) was added EXAMPLE 271 (0.300 g, 0.666 mmol). A stock solution of lhydroxybenzotriazole in N,N-dimethylformamide (3 mL, 0.ii M) was added to the reaction vessel fol!owed by approximately 0.97 g of the polymer bound carbodiimide resin (1.38 mmol/g). Additional N,N-dimethylformamide (2 mL) was then added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for 15 minutes• N- Methylamine in tetrahydrofuran (0.50 mL, 0.999 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with tetrahydrofuran (30 mL) and treated with approximately 2.0 g of polyamine resin (2.63 mmol/g) and approximately 3.6 g of methylisocyanate functionalized polystyrene (i.i0 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature for 4 hours. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were rinsed with tetrahydrofuran (2 x i0 mL) • The filtrate was evaporated by blowing N 2 over the vial while heating (60 °C) in a reaction block (KEM-Lab Parallel Reactor) to give an off-white solid (0.189 g, 61%). iH NMR (400 MHz, DMF-d 6 ) 6 8.56 (br d, J = 4.16 Hz, IH) , 8.05-7.76 (m, 3H) , 7.66 (t, J = 7.79 Hz, IH) , 7.56-7.19 (m, 3H) , 6.74 (s, IH) , 5.43 (s, 2H) , 3.46 (s, 3H) , 2.03 (s, 3H). ES-HRMS m/z 463.0476 (M+H C 21 HI BrF 2 N 2 0 3 requires 463.0463). preparation of Example 274-289 By following the method of Example 273 and replacing Nmethylamine with the appropriate amine, the compounds of Examples 274-289 are prepared. The deprotection of the protected intermediates was accomplished with 4N HCI in dioxane to afford the compounds as their hydrochloride salts. Compound% M+H ES-HRMS R1 R2 MF No. Yield Requires m/z Ex. 274 CH2CH2N-HCH2 CH2NH92.8 C 24 H 22 BrF 2 N 3 0 3 518. 0885 518.0865 Ex. 275 H CH2 CH2NH2 95.7 CnH, 0 BrF 2 N 3 0 3 492 . 0729 4 92.0711 Ex. 276 H CH2CH2CH2NH2 97.8 C 23 H 22 BrF 2 N O 3 506 . 0885 506.0889 Ex. 277 H OH 91.0 C 20 H sBrF 2 N 2 0 4 465.0256465.0278 Ex. 278 CH3 CH3 67.7 CnH:gBrF 2 N=O 477 . 0620 477.0626 Ex. 279 CH2CH20CH2CH2086.7 C 24 HnBrF 2 N 2 0 519. 0726 519.0696 Example 290 O O 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl] benzamide EXAMPLE 271 (2.00 g, 4.44 mmol) and 2-chloro-4,6-dimethoxyI, 3,5-triazine (0.94 g, 5.33 mmol) were suspended in tetrahydrofuran (20 mL) . 4-Methylmorpholine (1.5 mL, 13.32 mmol) was added. The resulting mixture was stirred for 1.5 hours at room temperature. NH 4 OH (i0 mL, 148.00 mmol) was added and the reaction was stirred for 0.5 hours at room temperature. H 2 0 (50 mL) and tetrahydrofuran (50 mL) were added and the organic layer was separated. The aqueous phase was extracted with ethyl acetate (75 mL) and the combined organics were washed with saturated Na 2 CO] (50 mL), IN HCI (50 mL) , and brine (50 mL) . The organic phase was dried over Na SO 4 and evaporated. The resulting solid was washed with diethyl ether to give a white solid (1.86 g, 93%). IH NMR (400 MHz, DMF-dG) 6 8.20 (br s, IH) , 8.10-8.07 (m, IH), 7.79 (s, IH), 7.79 (app q, J = 7.83 Hz, IH), 7.66 (app t, J = 7.79 Hz, IH) , 7.57-7.54 (m, IH) , 7.46 (br s, IH) , 7.36-7.19 (m, 2H) , 6.74 (s, IH) , 5.43 (s, 2H) , 2.04 (s, 3H) . ES-HRMS m/z 449.0307 (M+H C 20 HIsBrF 2 N 2 0 3 requires 449.0307). Example 291 3_[ 3_chl 0 r 0-4-[(2,4-diflu 0 r 0 benzyl)oxy]-6-methyl-2-oxopyridin- 1 (2H)-yl]benzoic acid Step i: Preparation of methyl 3-[3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]benzoate The product from step 2, Example 271 (4.54 g, 11.78 mmol) and N-chlorosuccinimide (1.65 g, 12.37 mmol) were suspended in dichloromethane (12 mL). Dichloroacetic acid (0.I0 ml, 1.22 mmol) was added and the reaction mixture was stirred overnight at 40 °C. The reaction was cooled to room temperature and a precipitate formed. The precipitate was collected by filtration and washed with dichloromethane {3 x i0 mL) to afford a white solid (1.75 g, 35%). The filtrate was concentrated and subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) to afforded an off white solid (1.29 g, 26%). The two solids were then combined. 1.96 (s, 3H). ES-H S m/z 420.0783 (M÷H C 21 HI 6 C!F 2 N0 4 requires 420.0809). Step 2: Methyl 3-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]benzoate ( from step I) (2.90 g, 6.91 mmol) was dissolved in methanol (5 mL) and tetrahydrofuran (12 mL) . 4N NaOH (4.3 mL, !7 27 mmol) was added. The resulting mixture was stirred for 1.5 hours at room temperature. The reaction was acidified (pH-2) with 4N HCI. The precipitate was collected by filtration to afford an off white solid (2.36 g, 84%). IH NMR (400 MHz, DMSO-dG ) 6 8.01 (dt, J = 1.41, 7.65 Hz, IH), 7.76 (app t, J = 1.68 Hz, IH), 7.69-7.53 (m, 3H), 7.36-7.14 (m, 2H), 6.69 (s, IH), 5.32 (s, 2H), 1.93 (s, 3H). ES-HRMS m/z 406.0662 (M+H C 20 HI 4 CIF 2 N0 4 requires 406.0652). Example 292 C I0 O o H 3-chloro-4- [(2,4-difluorobenzyl)oxy] -i- [3- (hydroxymethyl phenyl ] - 6 -methy!pyridin2 (IH) -one The starting material chlorosuccinimide (0.214 dichloromethane (15 mL). (0.550 g, 1.540 mmol) and N- g, 1.602 mmol) were suspended in Dichloroacetic acid (0.01 ml, 0.154 mmol) was added and the reaction mixture heated to 40 °C for hours. The reaction was cooled to room temperature and precipitate formed. The precipitate was collected filtration and washed with dichloromethane (3 x I0 mL) afford a white solid (0.286 g, 47%). IH N-MR (400 MHz, DMSO-d 7.38 (app q, J = 7.35 Hz, IH), 7.30-7.24 (m, 2H), 7.00 (br IH), 6.85 (app dt, J = 2.37, 6.24 Hz, IH), 6.82-6.67 (m, 6.01 (s, IH) , 5.07 (s, 2H) , 4.48 (d, J = 5.24 Hz, 2H) , (app d, J = 0.40 Hz, 3H) . ESHRMS m/z 392.0885 C 20 HI CIF 2 N0 3 requires 392.0860). Example 293 O 1 - [ 3 - ( aminomethyl ) phenyl ] - 3 - bromo4 - [ ( 2,4 - di f luorobenzyl ) oxy] 6 - methylpyridin2 (IH) - one Step i: Preparation of I- [3- (chloromethyl)phenyl]-4- [ difluorobenzyl) oxy] -6-methylpyridin-2 (IH) -one. dissolved in N,N-dimethylformamide (45 mL). The reaction mixture was stirred at room temperature for 1 hour and then dichloromethane (90 mL) was added. The alcohol (5.72 g, 15.99 mmol) was then added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane (200 mL) and the organic phase was washed with H 2 0 (200 mL), saturated Na 2 C0 3 (200 mL), IN HCI (200 mL), and brine (200 mL) . The organic phase was dried over MgS0 4 and evaporated to give an orange solid (5.95 g, 99%). Step 2: Preparation of i- [3-(aminomethyl)phenyl]-4-[(2,4difluorobenzyl)oxy]-6methylpyridin-2(iH)-one. l-[3-(chloromethyl)phenyl]-4-[(2,4-difluorobenzyl)oxy]-6_ methylpyridin-2(IH)-one from step 1 (I.00 g, 2.66 mmol) was suspended in methanol (5 niL). The suspension was then brought to -78 °C and NH 3 was bubbled through the reaction mixture for i0 minutes. The reaction was then slowly allowed to warm to room temperature and stirred at room temperature for 4 days. The reaction was concentrated and the residue taken up in CH 2 C1 2 and filtered to remove excess salt. The filtrate was concentrated to afford a tan solid (0.94 g, 99%). Step 3: Preparation of title compound 1-[3methylpyridin2 (IH) -one from step 3 (3.89 g, I0.93 mrnol) suspended in acetonitrile (42 mL) was cooled in an ice-bath. N-bromosuccinimide (2.04 g, 11.47 mmol) was added and the icebath was removed. The reaction mixture was stirred for 1.5 hours at room temperature. The reaction was diluted with acetonitrile (I00 mL) and the precipitate that formed was collected by filtration and washed with acetonitrile (3 x mL) to afford an off-white solid (2.74 g, 58%). H NMR (400 MHz, DMSO-d 6 ) 6 7.67-7.59 (m, 3H), 7.34-7.31 (m, 2H), 7.04 (app t, J = 8.72 Hz, 2H) , 7.05-6.88 (m, 2H) , 6.13 (s, IH) , 5.30 (s, 2H), 3.95 (s, IH), 2.01 (s, 3H) . ES-HRMS m/z 435.0538 (M+H C 20 HITBrF 2 N 2 0 2 requires 435.0514). Example 294 O N- { 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2 - oxopyridin1 (2H) -yl ] benzyl } methanesul fonamide To a reaction vessel (borosilicate culture tube) was added EXAMPLE 293 (0.200 g, 0.459 mmol) and N,N-dimethylformamide (4 mL). A stock solution of 4-methylmorpholine in N,Ndimethylformamide (1.8 mL, 1.0 M) was added to the reaction vesse! and the parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RgM at =oom temperature for i0 m±nu es. stocky resolution methanesulfonyl chloride in N,N-dimethylformamide (4.50 mL, 0.15 M) was then added to the reaction vesse! and the reaction apparatus was orbitally shaken at room temperature for 2 hours. At this time the reaction was diluted with dich!oromethane (4 mL) and treated with approximately 2.1 g of polyamine resin (2.63 mmol/g) and approximately 0.8 g of methy!isocyanate functionalized polystyrene (1.7 mmo!/g) and the orbital shaking was continued at 200 RPM at room temperature overnight. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were rinsed with dichloromethane (2 x 5 mL). The filtrate was evaporated by blowing N 2 over the vial while heating (60 °C) in a reaction b!ock (KEM-Lab Parallel Reactor) to give a yellow solid (0.190 g, 81%). IH NMR (400 MHz, CD 3 OD) 6 7.63 (app q, J = 7.00 Hz, IH), 7.56-7.50 (m, 2H), 7.25 (m, IH), 7.16 (dt, J = 1.94, 7.25 Hz IH), 7.04 (app t, J = 8.59 Hz, 2H), 6.58 (s, IH) , 5.34 (s, 2H), 4.30 (s, 2H), 2.87 (s, 3H), 2.03 (s, 3H) . ES-HRMS m/z 513.0313 (M,H C 21 HIgBrF 2 N 2 0 4 S requires 513.0290). Preparation of Example 295-296 By following the method of Example 294 and replacing methanesulfonyl chloride with the appropriate acid chloride, the compounds of Examples 295-296 are prepared. Compound% M+H ES - HRMS R MF No. Yield Requires m/z Ex. 295 CH 3 78.0 C =HIgBrF 2 N 2 0 3 477.0620 477. 0640 Ex. 296 OCH 3 84.0 C 22 HIgBrF 2 N O 4 493.0569 493.0591 Example 297 N-{3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl] benzyl } -2-methoxyacetamide To a reaction vessel (borosilicate culture tube) was added approximately 2.87 g of polymer bound carbodiimide resin (0.96 mmol/g) followed by a stock solution of methoxyacetic acid (8.0 mL, 0.i0 M) in N,N-dimethylacetamide. A stock solution of l-hydroxybenzotriazole in N,N-dimethylacetamide (3.0 mL, 0.i0 M) and N-methylmorpholine (6.0 mL, 0.i0 M) in 1,2dichloroethane were added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for 4 hours. A stock solution of EXAMPLE 293 in N,N-dimethylacetamide (5.0 mL, 0.10 M) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with 1,2-dich!oroethane (I0 mL) and treated with approximately 1.70 g of polyamine resin (2.63 mmol/g) and approximately 0.84 g of methylisocyanate functionalized polystyrene (1.50 mmol/g) and the orbita! shaking was continued at 200 RPM at room temperature for 4 hours. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were rinsed with N,N-dimethylacetamide (2 x 5 mL) . The filtrate was evaporated by blowing N 2 over the vial while heating (60 °C) in a reaction block (KEM-Lab Parallel Reactor) and subjected to chromatography (silica gel, ethyl acetate with 10% me hanol/hexanes) afforded an off white solid (0.081 g, 28%). IH NMR (400 MHz, DMF-d 6 ) 7.59 (q, J = 7.65 Hz, IH) , 7.46 (app t, J = 7.55 Hz, IH), 7.40-7.37 (m, IH), 7.11-7.07 (m, 2H), 7.00 (t, J = 8.56 Hz, 2H), 6.54 (s, IH), 5.30 (s, 2H) , 4.43 (s, 2H), 3.88 (s, 2H), 3.35 (app d, J = 0.80 Hz, 2H), 1.97 (s, 3H) . ES-HRMS m/z 507.0699 (M+H C 23 H 21 BrF 2 N 2 0 4 requires 507.0726). Preparation of Examples 298-300 By following the method of and replacing methoxyacetic acid with the appropriate acid, the compounds of Examples 298-300 are prepared. The deprotection of the protected intermediates was accomplished with 4N HCI in dioxane or 1 M K 2 CO 3 in methanol to afford the compounds as hydrochloride salts. Compound % M+H ES-HRMS R MF No. Yield Requires m/z Ex. 298 CH 2 OCOCH 35.5 C 24 H 21 BrF 2 N=Os 535 . 0675 535 . 0686 Ex. 299 CHzN-H 32.6 C 22 H 0 BrF 2 N 3 0 3 492.0729492.0744 CH 2 OH 33.4 C 22 HI..BrF 2 N 2 0 4 493.0569493.0578 Ex. 300 Example 301 O H N' ° { 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6 -methyl -2- oxopyridin1 (2H) -yl] benzyl } -N, N-dimethylurea Step i: Preparation of 4-nitrophenyl 3-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]benzylcarbamate. l-[3-(aminomethyl)phenyl]-3-bromo-4-[(2,4-difluorobenzyl oxy]- 6-methylpyridin-2(iH -one (1.08 g, 2.48 mmol) was suspended in dichloromethane (7.5 mL). Pyridine was added (0.222 mL, 2.74 mmol) . After stirrlng for i0 minutes at room temperature, a stock solution of 4-nitrophenyl chloroformate (5.0 mL, 0.50 M) in dichloromethane was added dropwise. After stirring for 4.5 hours at room temperature, a stock solution of 4-nitrophenyl chloroformate (2.5 mL, 0.50 M) in dichloromethane was again added dropwise and stirring continued at room temperature overnight. The reaction mixture was concentrated and subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) afforded a yellow solid (0.85 g, 57%). Step 2: Preparation of title compound To a reaction vessel (borosilicate culture tube) was added 4-nitrophenyl 3-[3bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]benzylcarbamate (from step i) (0.150 g, 0.250 mmol) and dichloromethane (2.5 mL). The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for 15 minutes. A stock solution of N,N-dimethylamine in tetrahydorfuran (0.15 mL, 2.0 N) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. The reaction mixture was concentrated and subjected to chromatography (silica gel, ethyl acetate with 10% me thanol/he a es ) which afforded an off white solid (0.065 (s, 3H) . ES-HRMS m/z 506.0848 (M+H C 23 H= 2 BrF 2 N 3 0 3 requires 5O6.0885). Preparation of Examples 302-303 HNAN-R 1 I R 2 O By following the method of Example 301 and substituting N,Ndimethylamine with the appropriate amine, the compounds of Examples 302-303 are prepared. Compound% M+H ES -HRMS E 1 R 2 MF No. Yield Requires m/z Ex. 302 52.3 492. 0729 492. 0737 Ex. 303 50.7 548.0991 548.O962 Example 304 oxopyridin1 (2H) -yl ] benzyl }urea To a reaction vessel (borosilicate culture tube) was added EXAMPLE 293 (0.200 g, 0.459 mmol) and tetrahydrofuran (4.0 mL). A stock solution of 4-methylmorpholine in tetrahydrofuran (i.8 mL, 1.0 M) was added to the reaction vessel and the parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for I0 minutes. A stock solution of trimethylsilyl isocyanate in tetrahydrofuran (4.0 mL, 0.2 M) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature for two hours. At this time the reaction was diluted with tetrahydrofuran (4.0 mL) and the resulting precipitate collected by filtration. The solid was then washed with tetrahydrofuran (3 x 5 mL) to afford a white solid (0.214 g, 97%). IH NMR (400 MHz, CD 3 OD) 6 7.72 (app q, J = 7.83 Hz, IH), 7.55 (app t, J = 8.06 Hz, IH), 7.46 (d, J = 7.52 Hz, IH), 7.25-7.14 (m, 4H), 6.65 (s, IH), 5.65 (app t, J = 0.80 Hz, IH) , 5.40 (s, 2H) , 4.38 (s, 2H) , 2.05 (s, 3H) . ES-HRMS m/z 478.0594 (M+H C 21 HIsBrF 2 N 3 0 3 requires 478.0572). Example 305 [(dimethylamino)methy!]phenyl)-6-methylpyridin-2(iH)-one Step i: Preparation of 4-[(2,4-difluorobenzyl)oxy]-l-{3- [(dimethylamino)methyl}phenyl }-6-methylpyridin-2(!H)-one. i-[3-(chloromethyl)phenyl]-4-[(2,4-difluorobenzyl)oxy]-6- methylpyridin-2(iH)-one (from step 1 of the synthesis of EXAMPLE 293) (0.500 g, 1.330 mmol) was suspended in a stock solution of N,N-dimethylamine in methanol (2.0 mL, 2.0 M) and stirred overnight a5 room temperature. Reaction was concentrated and the residue partitioned between H 2 0 (25 mL) and ethyl acetate (25 mL) . The aqueous layer was further extracted with ethyl acetate (2 x 30 mL), and the combined organics were washed with brine (30 mL), dried over MgSO 4 , and concentrated to afford an off-white solid (0.508 g, 99%). Step 2: Preparation of the title compound 4-[(2,4difluorobenzyl)oxy]-!-{3-[(dimethylamino)methyl]phenyl}-6methylpyridin-2(iH)-one from step 1 (0.200 g, 0.521 mmol) was suspended in acetonitrile (2.5 mL) and cooled in an ice-bath. N-bromosuccinimide (0.097 g, 0.547 mmol) was added and the ice-bath was removed. The reaction mixture was stirred for 1.5 hours at room temperature. The reaction was diluted with acetonitrile (i00 mL) . The precipitate that formed was collected by filtration and washed with acetonitrile (3 x mL) to afford a yellow solid (0.160 g, 66%). Chromatography (C-18, acetonitrile/H 2 0 with 0.1% trifluoroacetic acid, followed by chromatography silica gel, ethyl acetate with 10% methanol/hexanes) afforded an off-white solid (0.024 g, 10%). IH NMR (400 MHz, CD 3 OD) 6 7.68 (app q, J = 7.85 Hz, IH), 7.58 (app t, J = 7.65 Hz, IH), 7.50 (app d, J = 7.85 Hz, IH), 7.257.05 (m, 4H), 6.63 (s, IH), 5.39 (s, 2H), 3.61 (app q, J = 12.08 Hz, 2H), 2.32 (s, 6H), 2.08 (s, 3H). ES-HRMS m/z 463.0782 (M+H C 22 H 21 BrF 2 N 2 0 2 requires 463.0827). Example 306 O.. O N- {4- [4- (benzyloxy) -3-bromo-2-oxopyridin-I (2H) - yl] benzyl }acetamide l-[4-(aminomethyl phenyl]-4-(benzyloxy)-3-bromopyridin-2(iH)- one hydrochloride (0.150 g, 0.389 mmol) was dissolved in N,Ndimethylformamide (3.5 mL). A stock solution of 4methylmorpholine in N,N-dimethylformamide (1.5 mL, 1.0 M) was added and the reaction stirred at room temperature for i0 minutes. A stock solution of acetyl chloride in N,Ndimethylformamide (3.0 mL, 0.2 M) was then added to the reaction vesse! and the reaction apparatus was orbitally shaken at 200 RPM for 2 hours at room temperature. At this time the reaction was diluted with dichloromethane (4 mL) and treated with approximately 1.8 g of polyamine resin (2.63 mmol/g) and approximately 0.8 g of methylisocyanate functionalized polystyrene (1.7 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature overnight. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were further rinsed with dichloromethane (3 x 5 mL) and combined with the partially concentrated filtrate. The resulting filtrate was concentrated by blowing N 2 over the vial while heating (60 °C) in a reaction block (KEM-Lab Parallel Reactor) to give an off-white solid (0.083 g, 50%). IH N-MR (400 MHz, CD 3 OD) 6 7.59 (d, J = 7.79 Hz, IH) , 7.48-7.29 (m, 9H) , 6.55 (d, J = 7.79 Hz, IH) , 5.35 (s, 2H) , 4.39 (s, 2H) , 1.98 (s, 3H) . ES-HRMS m/z 427.0625 (M+H C 21 HIgBrN 2 0 3 requires 427.0652). Example 307 N- {4- [4- (benzyloxy) - 3-bromo-2-oxopyridin1 (2H) -yl] benzyl } -2hydroxyacet amide To a reaction vessel (borosilicate culture tube) was added approximately 1.95 g of polymer bound carbodiimide resin (0.96 mmol/g) followed by a stock solution of glycolic acid (5.8 mL, 0.i0 M) in N,N-dimethylacetamide. A stock solution of l-hydroxybenzotriazole in N,N-dimethylacetamide (0.4 mL, 0.i0 M) and N-methylmorpholine in 1,2-dichloroethane (3.9 mL, 0.I0 M) were added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for 2 hours. A stock solution of i- [4- (aminomethyl)phenyl]-4- (benzyloxy)-3-bromopyridin-2(iH)-one hydrochloride in N,Ndimethylacetamide (0.05 M, 7.8 mL) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with 1,2-dichloroethane (8 mL) and treated with approximately 1.17 g of polyamine resin (2.63 mmol/g) and approximately 0.58 g of methylisocyanate functionalized polystyrene (1.50 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature for 4 hours. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproduct by titration and collection into a. vial. After partial evaporation the insoluble byproducts were rinsed with N,N-dimethylacetamide (2 x 5 mL) and combined with the partially concentrated filtrate. The filtrate was concentrated by blowing N 2 over the vial while heating (60 °C) in a reaction block (KEM-Lab Parallel Reactor) and subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) which afforded an off white solid (0.081 g, 21%). IH NMR (400 MHz, CD 3 OD) 6 7.55-7.30 (m, 10H), 6.51 (d, J = 7.85 Hz, IH) , 5.37 (s, 2H) , 4.52 (s, 2H) , 4.08 (s, 2H) . ES- HRMS m/z 443.0605 (M+H CnHIgBrN 0 4 requires 443.0601). Example 308 O 3-br 0 m 0-4-[(2,4-diflu 0 r 0 benzyl) 0 xy]-6-methyl-l-(2-morpholin-4ylethyl)pyridin-2(IH)-one 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyipyridin-2(IH)-one (0.i00 g, 0.303 mmol), cesium carbonate (0.296 g, 0.909 mmol) , and 4-(2-chloroethyl)morpholine (0.059 g, 0.394 mmol) were suspended in acetonitrile (4 mL). The reaction was stirred at °C overnight. H 2 0 (25 mL) was added and the resulting precipitate was collected by filtration. The solid was subjected to chromatography (silica gel, ethyl acetate with tOM methanol afforded a off -white solid (0.044) 30 ). i 3H) . ES-HRMS m/z 443.0743 (M+H C=gH 2 !BrF 2 NcO 3 requires 443.0776). Example 309 ethyl 3- [4- (benzyloxy) -3-bromo-2-oxopyridin-i (2H) - yl]propanoate 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin- 2(!H)-one (0.50 g, 1.78 mmol) and cesium fluoride (0.0027 g, 0.178 mmol) were suspended in tetrahydrofuran (i0 mL) fol!owed by dropwise addition of tetraethylortho silicate (0.37 g, 1.78 mmol) at room temperature. After stirring for I0 minutes at room temperature, ethyl acrylate (0.23 g, 2.32 mmol) was added dropwise and the reaction stirred at room temperature overnight. The reaction mixture was filtered through a pad of Celite®. The filtrate was concentrated and the resulting residue subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) to afford a white solid (0.62 g, 380.0523 (M+H C 17 HIsBrNO 4 requires 380.0492). Example 310 o o methyl 3- [4- (benzyloxy) -3-bromo-2-oxopyridin-I (2H) - yl ] propanoate 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin2(iH)-one (5.00 g, 17.85 mmol) and cesium fluoride (0.27 g, 1.78 mmol) were suspended in tetrahydrofuran (50 mL) followed by dropwise addition of tetramethylortho silicate (2.70 g, 17.85 mmol) at room temperature. After stirring for i0 minutes at room temperature, methyl acrylate (2.00 g, 23.20 mmol) was added dropwise and the reaction stirred at room temperature for 48 hours. The reaction mixture was filtered through a pad of Celite®. The filtrate was concentrated and the resulting residue subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) to afford a white solid (6.10 g, 93%). IH NMR (400 MHz, CDCI ) 6 7.42 (d, J = 7.65 Hz, IH), 7.41-7.29 (m, 5H), 6.04 (d, J = 7.65 Hz, IH), 5.20 (s, 2H), 4.17 (t, J = 5.91 Hz, 2H), 3.63 (s, 3H), 2.85 (t, J = 5.91 Hz, 2H) . ES-HRMS m/z 366.0350 (M+H CI 6 HIGBrNO 4 requires 366.0335). Example 311 F HN F N-[3-bromo-l-(3-fluorobenzyl)-2-oxo-l,2-dihydropyridin-4-yl]- 2,6-difluorobenzamide Step I: Preparation of 3,4-dibromo-l-(3-fluorobenzyl)pyridin2(iH)-one. O 3-bromo-l-(3-fluorobenzyl)-2-oxo-l,2-dihydropyridin-4-yl trifluoromethanesulfonate (2.00 g, 4.65 mmol), KBr (5.53 g, 46.49 mmol), and 18-Crown-6 (0.i0 g, 0.38 ,Lmol) were dissolved in N,N-dimethylacetamide (26 mL). The reaction mixture was then heated at reflux for 16 hours. The reaction was concentrated and the resulting residue was partition between water (50 mL) and ethyl acetate (3 X 50 mL) . The combined organics were washed with H 2 0 (2 X 30 mL), brine (50 mL), dried over MgSO 4 , concentrated, and subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexane) to afford a brown solid (0.850 g, 51%). Step 2: Preparation of 4-azido-3-bromo-l-(3fluorobenzyl) pyridin-2 (IH) -one. O Sodium azide (1.08 g, 16.62 mmol) was suspended in N,Ndimethylformamide CI0 mL) and a stock solution of 3,4dibromo~l-(3-fluorobenzyl)pyridin-2(IH)-one (from step i) in N,N-dimethylformamide (33.0 mL, 0.33 M) was added and the resulting mixture was heated to 60 °C for 4 hours. Ice water (30 mL) was added and the aqueous layer was extracted with ethyl acetate (4 X 50 mL). The combined organics were washed with H 2 0 (3 X 50 mL), brine (2 X 25 mL), dried over MgSO 4 , concentrated, and subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexane) to afford an off-white solid (3.50 g, 98%). Step 3: Preparation of 4-amino-3-bromo-l-(3fluorobenzyl)pyridin-2(iH)-one hydrochloride O 4-azido-3-bromo-l-(3-fluorobenzyl)pyridin-2(iH)-one (from step 2) (4.00 g, 12.38 mmol) was suspended in ethyl acetate (300 mL) and Fe (2.07 g, 37.14 mmol) was added. A stock solution of NH 4 CI in H 2 0 (300 mL, 0.2 M) was added and the reaction mixture was stirred at room temperature for 36 hours. The reaction was filtered through a pad of Celite® and concentrated. The resulting solid was dissolved in ethyl acetate (150 mL) and washed with water (3 X 50 mL), brine (50 mL), dried over MgS0 4 , and concentrated. IH NMR (400 MHz, CD 3 OD) 6 7.38-7.29 (m, 2H), 7.05 (d, J = 7.79 Hz, IH), 6.99 (d, J = 8.99 Hz, 2H), 6.03 (d, J = 7.39 Hz IH), 5.09 (s, 2H). ESHRMS m/z 297.0023 (M+H C 20 HI BrF 2 N 2 0 2 requires 297.0033). Step 4: Preparation of the title compound 4-amino-3-bromoi- (3-fluorobenzyl)pyridin-2(iH)-one (from step 3) (0.30 g, 1.01 mmol) and 4-dimethylaminopyridine (0.002 g, 0.01 mmol) were suspended in acetonitrile (5 mL) followed by dropwise addition of triethylamine (0.2 mL, 1.41 mmol). This reaction mixture was stirred for i0 minutes at room temperature before being cooled to 0 °C. 2,6-difluorobenzoyl chloride (0.37 g, 2.12 mmol) was added dropwise and the reaction was heated at reflux overnight. The reaction was cooled to room temperature and IN NaOH (I0 mL) was added. The reaction was then stirred for 45 minutes at room temperature. The reaction mixture was extracted with ethyl acetate (3 x 25 mL) and the organic layer washed with IN NaOH (2 X 25 mL), H 2 0 (until pH neutral), brine (50 mL), dried over MgSO concentrated, and subjected to chromatography (on C-18, acetonitrile/ H 2 0 with 0.1% trifluoracetic acid) to afford a white solid (0.19 g, 43%). IH NMR (400 MHz, CDCI 3 ) 6 8.42 (br s, IH), 7.67 (d, J = 7.65 Hz, IH), 7.49 (app it, J = 6.31, 8.60 Hz, IH), 7.33-28 (m, 2H), 7.10-6.97 (m, 5H), 5.17 (s, 2H) . ES-HRMS m/z 437.0083 (M+H C 19 HI BrF 3 N 2 0 2 requires 437.0107). difluorobenzyl) oxy] - 6-methylpyridin-2 (IH) -one Step I: Preparation of l-(4-bromo-2,6-difluorophenyl)-4hydroxy-6-methylpyridin-2(iH)-one F Br 4-Hydroxy-6-methyl-2-pyrone (30.0 g, 238 mmol) and 4-bromo2,6-difluoroaniline (49.5 g, 238 mmol) were suspended in 50 ml of 1,2-dichlorobenzene in a 250 ml, 3-necked, round bottom flask equipped with a J-Kem temperature controller probe, a Dean-Stark trap, and a heating mantle. The reaction was heated to 165°C for 15 minutes, during which, water and some 1,2-dichlorobenzene was collected in the Dean-Stark trap. The reaction was allowed to cool to about 80°C. The flask was placed in an ice bath and about 25 ml of toluene was added and stirred. After about i0 minutes, a precipitate formed. The precipitate was filtered and washed 3 times with toluene, 3 times with hot water to remove excess pyrone, and dried in vacuo to give a tan solid (22.1 g, 29%). IH NMR (400 MHz, minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 316 (M+H) . ES-HRMS m/z 315.9779 (M+H calcd for C 12 HsBrF 2 NO 2 requires 315.9779) . Step 2 : Preparation of i- (4-bromo-2,6-difluorophenyl) -4- [ (2,4-difluorobenzyl) oxy] -6-methylpyridin-2 (IH) -one i- (4-bromo-2,6-difluorophenyl) -4-hydroxy6-methylpyridin2 (IH)-one ( from Step i) (5.0 g, 15.8 retool) was stirred briskly at room temperature with 2,4-difluorobenzyl bromide (2.23 ml, 17.4 retool) and K 2 CO] (3.27 g, 23.7 retool) in 50 ml of dimethylformamide. After stirring overnight, the reaction was poured quickly into 900 ml of cold water. The resulting precipitate was filtered and washed with water and hexane. The product was purified using a Biotage silica chromatography system using 20% ethyl acetate/hexanes to give a beige solid (4.32 g, 62%). IH NMR (400 MHz, CDCI 3 ) 6 7.41 (app q, J = 6.31 Hz, IH), 7.25 (dd, J = 8.33, 1.74 Hz, 2H), 6.91 (dt, J = 9.2, 0.8 Hz, IH), 6.86 (dt, J = 9.2, 0.8 Hz, IH), 5.95 (d, J = 2.56 Hz, IH) , 5.92 (dd, J = 2.56, 0.94 Hz, IH) , 5.01 (s, 2H) , 1.98 (s, 3H) . LC/MS, tr = 3.04 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES- MS m/z 442 (M÷H) . ES-HRMS m/z 442. 0057 (M+H calcd for C 19 HnBrF 4 NO 2 requires 442.0060) . Step 3: Preparation of the title compound I- (4-bromo-2,6di f luorophenyl ) - 4 - [ ( 2,4 -d f uorobenzyl ) oxy]- 6 - met:h ip r 2(iH)-one ( from Step 2) (500 mg, 1.13 mmol) was stirred at room temperature with N-bromosuccinimide (221 mg, 1.24 mmol) in 5 ml of CH 2 C1 2 for 1.5 hours. The reaction was evaporated on a rotary evaporator and the resulting solid was washed 4 times with acetonitrile and dried in vacuo to yield a white solid (478 mg, 92%). IH NMR (300 MHz, CDCI 3 ) 6 7.62 (app q, J = 6.64 Hz, IH), 7.31 (d, J = 6.85 Hz, 2H), 7.01 (app t, J = 8.36 Hz, IH), 6.96 (dt, J = 9.46, 2.21 Hz, IH), 6.19 (s, IH), 5.30 (s, 2H), 2.10 (s, 3H) ; LC/MS, tr = 3.17 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 520 (M+H) . ES-HRMS m/z 521.9134 (M+H calcd for C 19 HnBr 2 F 4 NO 2 requires 521.9146). Ex. 313 F F 3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methylI- (2,4,6trifluorophenyl ) pyridin2 (IH) - one The title compound was produced essentially as in Example 313, using 2,4,6-trifluoroaniline instead of 4-bromo-2,6difluoroaniline. IH NMR (300 MHz, CDCI ) 6 7.62 (app q, J = 7.79 Hz, IH), 7.01 (app dt, J = 8.26, 2.01 Hz, IH) , 6.95 - 6.85 (m, 3H), 6.19 (s, IH), 5.30 (s, 2H), 2.11 (s, 3H) ; LC/MS, tr = 2.81 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 460 (M+H). ES-HRMS m/z 459.9954 (M+H calcd for C 19 HIIBrFsNO 2 requires 459.9966). tri f luorophenyl ) pyridin2 (IH) -one 4- [(2,4-difluorobenzyl)oxy]-6-methyl-l-(2,4,6trifluorophenyl)pyridin-2(IH)-one (350 mg, 0.92 mmol) was refluxed with N-chlorosuccinimide (147 mg, i.i mmol) and dichloroacetic acid (0.038 ml, 0.46 mmol) in 5 ml of CH 2 C1 2 overnight. The reaction was evaporated on a rotary evaporator and the resulting solid was washed 4 times with acetonitrile and dried in vacuo to yield a white solid (217 mg, 57%). IH NMR (300 MHz, CDCI 3 ) 6 7.60 (app q, J = 7.75 Hz, IH), 7.00 (app dt, J = 8.23, 2.05 Hz, IH), 6.93 - 6.86 (m, 3H), 6.22 (s, IH), 5.30 (s, 2H), 2.12 (s, 3H) ; LC/MS, tr = 2.78 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 416 (M+H) . ES-HRMS m/z 416.0472 (M+H calcd for C 19 HnCIFsNO 2 requires 416.0471). 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-l- (2,4,6trifluorophenyl)pyridin-2(iH)-one Step I: Preparation of 4- [(2,4-difluorobenzyl)oxy]-6- (hydroxymethyl) -I- (2,4,6-trif!uorophenyl) pyridin-2 (IH) -one F F OH 4- [ (2,4-Difluorobenzyl) oxy] -6-methyl-i- (2,4,6trifluorophenyl)pyridin-2(1H)-one (9.0 g, 23.6 mmol) was heated to 135°C overnight with SeO 2 (13.1 g, 118 mmol) in 75 ml of 1,4-dioxane in a 350 ml sealed glass pressure vessel. The reaction mixture was cooled and placed on a plug of silica gel and washed with 5% methanol in CH 2 C1 2 . The filtrate was evaporated and the resulting solid was washed with diethyl ether and dissolved in hot ethyl acetate. The insoluble Se salts were filtered off and the organic layer was evaporated. 7.01g (17.6 mmol) of a 3:1 ratio of aldehyde to desired alcohol was isolated. The mixture was stirred with NaBH 4 (802 mg, 21.2 mmol) in 30 ml of methanol at room temperature for 1 hour. The reaction was evaporated and CH 2 C1 2 and acetonitrile were used to dissolve the bulk of the solid. The remaining insoluble solid was filtered off. The organic layer was washed 3 times with NH 4 CI, dried over MgS0 4 and evaporated. The resulting solid was washed 3 times with diethyl ether and dried in vacuo to yield a light orange solid (4.35 g, 46%). IH (s, 2H) ; LC/MS, tr = 2.31 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 398 (M+H). Step 2: Preparation of the title compound . 4-[(2,4Difluorobenzyl)oxy]-6-(hydroxymethyl)-l-(2,4,6trifluorophenyl)pyridin-2(iH)-one ( from step I) (2.1 g, 5.28 mmol) was stirred at room temperature with N-bromosuccinimide (1.13 g, 6.34 mmol) in 5 ml CH 2 C1 2 for 2 hours. The reaction was evaporated on a rotary evaporator and the resulting solid was washed 4 times with acetonitrile and dried in vacuo to yield a white solid (1.35 g, 54%). iH NMR (300 MHz, CD 3 OD) 6 7.69 (app q, J = 6.65 Hz, IH), 7.20 (app t, J = 8.36 Hz, 2H), 7.09 (app t, J = 8.46 Hz, 2H), 6.88 (s, IH), 5.46 (s, 2H), 4.21 (s, 2H) ; LC/MS, tr = 2.48 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 476 (M+H) . ES-HRMS m/z 475.9907 (M+H calcd for C 19 HIIBrFsNO requires 475.9915). Ex. 316 OH F Cl O F 3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-l- (2,4,6trifluorophenyl)pyridin-2(iH)-one 4-[(2,4-Difluorobenzyl)oxy]-6-(hydroxymethyl)-l-(2,4,6_ trifluorophenyl)pyridin-2(iH)-one (2.1 g, 5.28 mmol) was refluxed with N-chlorosuccinimide (846 mg, 6.34 mmol) and dichloroacetic acid (0.87 ml, i0.56 mmol) in 5 ml CH 2 C1 2 overnight. The reaction was evaporated on a rotary evaporator and the resulting oil was triturated with diethyl ether to obtain a solid. The solid was washed 4 times with acetonitrile. Chromatography was done using a Biotage silica gel system with 60% ethyl acetate/hexanes. The recovery was poor from the column to give a white solid (109 rag, 5%). H NMR (300 MHz, CDaOD) 6 7.67 (app q, J = 7.85 Hz, IH), 7.24 - 7.06 (m, 4H), 6.90 (s, IH), 5.45 (s, 2H), 4.22 (s, 2H) ; LC/MS, tr = 2.71 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 432 (M+H). ES-HRMS m/z 432.0413 (M+H calcd for C 19 HuCIFsNO 3 requires 432.0420). Ex. 317 F F O F N 3-bromo-4- [ (2,4-difluorobenzyi) oxy] -i- (2,6-difluoro-4- morpholin-4-ylphenyl)-6-methylpyridin-2(iH)-one Step i: Preparation of 4-[(2,4-difluorobenzyl)oxy]-l-(2,6difluoro-4-morpholin-4-ylphenyl) -6-methylpyridin-2 (IH) -one trifluorophenyl)pyridin~2(iH)-one (870 rag, 2.28 retool) was heated to 100°C with K 2 CO (630 rag, 4.56 retool) in 5 ml of morpholine for 36 hours. The reaction was added to 200 ml of cold water and the resulting solid was washed with water and 50:50 diethyl ether/hexanes and dried in vacuo to give a beige solid (738 rag, 72%). IH NMR (400 MHz, CDCI 3 ) 6 7.41 (app q, J = 7.70 Hz, IH), 6.93 - 6.85 (m, 2H), 6.49 (d, J = 10.47 Hz, 2H) , 5.96 (d, J = 2.41 Hz, IH), 5.89 (d, J = 1.75 Hz, IH), 5.00 (s, 2H), 3.83 (t, J = 4.83 Hz, 4H), 3.19 (t, J = 4.84 Hz, 4H), 1.99 (s, 3H) ; LC/MS, tr = 3.09 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 449 (M+H). ES-HR/MS m/z 449.1485 (M+H calcd for C 2 aH 20 F 4 N 2 0 3 requires 449. 1483) . Step 2: Preparation of the title compound 4-[ (2,4Di fluorobenzyl ) oxy] - 1 - (2,6difluoro-4 -morpholin4 -ylphenyl ) -6 - methylpyridin-2(iH)-one ( from step i) (500 rag, 1.12 retool) was stirred at room temperature with N-bromosuccinimide (236 mg, 1.33 mmol) in 5 ml of CH 2 C1 2 for 2 hours. The reaction was evaporated on a rotary evaporator and the resulting oil was triturated with diethyl ether to obtain a solid. The solid was washed 4 times with acetonitrile and dried in vacuo to yield a white solid (171 rag, 29%). IH NMR (400 MHz, CDCI 3 ) 6 7.58 (app q, J = 7.74 Hz, IH), 6.96 (app t, J = 8.39 Hz, IH), 6.86 (dt, J = 9.46, 2.28 Hz, IH), 6.50 (d, J = 10.74 Hz, 2H), 6.09 (s, IH), 5.24 (s, 2H), 3.84 (t, J = 4.84 Hz, 4H), 3.20 (t, J = 4.83 Hz, 4H), 2.07 (s, 3H) ; LC/MS, tr = 3.18 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 527 (M+H) . ES-HRMS m/z 527.0570 (M+H calcd for C= 3 HIgBrF 4 N 2 0 3 requires 527.0588). methylpiperaz in1 -yl ) phenyl ] - 6 -methylpyridin2 (IH) - one The title compound was prepared essentially as in Example 317, using l-methylpiperazine instead of morpholine. IH NMR (400 MHz, CDCI ) 6 7.57 (app q, J = 7.79 Hz, IH), 6.96 (dr, J = 8.19, 1.88 Hz, IH), 6.86 (app dt, J = 9.44, 2.48 Hz, IH), 6.52 (d, J = 10.61 Hz, 2H), 6.14 (s, IH), 5.24 (s, 2H), 3.72 (br 4H), 3.51 (d, J = 11.27 Hz, 2H), 3.07 (br s, 2H), 2.85 (d, J 4.29 Hz, 3H), 2.06 (s, 3H) ; LC/MS, tr = 2.50 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 540 (M+H). ES-HRMS m/z 540.0930 (M+H calcd for C 24 H 22 BrF 4 N 3 0 2 requires 540.0904). methy!piperazin1 -yl ) phenyl ] - 6 -methylpyridin2 (IH) -one 4- [ (2,4-Difluorobenzy!) oxy] -i- [2,6-difluoro-4- (4- methylpiperazin-l-yl)phenyl]-6-methylpyridin-2(iH)-one (1.3 g, 2.82 mmol) was stirred at reflux with N-chlorosuccinimide (451 rag, 3.38 mmol) and dichloroacetic acid (0.17 ml, 1.41 mmol) in 6 ml CH 2 C1 2 overnight. LC-MS showed 33% completion. More Nchlorosuccinimide (271 mg, 2.23 mmol) was added and refluxed overnight. The reaction was evaporated on a rotary evaporator and the resulting oil was triturated with ethyl acetate to obtain a solid. The solid was washed 4 times with ethyl acetate and with diethyl ether and dried in vacuo to obtain a white solid (606 rag, 43%). IH NMR (400 MHz, DMSO-d 6 ) 6 7.66 (br q, J = 7.74 Hz, IH), 7.33 (br t, J = 9.00 Hz, IH), 7.16 (br t, J = 7.65 Hz, IH), 6.96 (d, J = 11.81 Hz, 2H), 6.79 (s, IH), 5.33 (s, 2H), 3.61 (br m, 4H), 3.25 (br m, 4H), 3.21 (br s, 3H), 2.04 (s, 3H) ; LC/MS, tr = 2.45 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 496 (M+H). ES-HRMS m/z 496.1400 (M+H calcd for C 24 H 22 CIF 4 N 3 0 2 requires 496.1409). Example 321 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-[4-(dimethylamino)-2,6difluorophenyl]-6-methylpyridin-2(iH)-one The title compound wasprepared essentially as described in Example 317, using dimethylamine instead of morpholine. IH NMR (400 MHz, CDCI 3 ) 6 7.59 (q, J = 7.74 Hz, IH), 6.95 (dt, J = 8.32, 1.61 Hz, IH), 6.85 (app dt, J = 9.54, 2.41 Hz, IH), 6.27 (d, J = ii.01 Hz, 2H) , 6.08 (s, IH), 5.23 (s, 2H) , 2.98 (s, 3H), 2.07 (s, 3H); LC/MS, tr = 3.35 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 485 (M+H). ES-HRMS m/z 485.0447 (M+H calcd for C 21 HITBrF 4 N 2 0 2 requires 485.0482). Example 322 F/'- ' N OH I 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-{2,6-difluoro-4-[(2hydroxyethyl) (methyl)amino]phenyl}-6-methylpyridin-2(iH)-one The title compound was prepared essentially as in Example 317, using 2-(methylamino)ethanol instead of morpholine. IH NMR (400 MHz, CDCI 3 ) 6 7.58 (q, J = 7.74 Hz, IH), 6.95 (dt, J = 8.24, 1.66 Hz, IH), 6.85 (app dt, J = 9.49, 2.37 Hz, IH), 6.35 (d, J = II.01 Hz, 2H), 6.10 (s, IH), 5.23 (s, 2H), 3.77 (t, J = 5.77 Hz, 2H), 3.45 (t, J = 5.78 Hz, 2H), 2.99 (s, 3H), 2.08 (s, 3H); LC/MS, tr = 2.96 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 515 (M+H) . ES-HRMS m/z 515.0576 (M+H calcd for CnHIgBrF 4 N 2 0 3 requires 515.0588) . Example 323 O B 3 - bromo1 - ( 3,5 - dibromo2,6 - di f luoro - 4 - hydroxyphenyl ) - 4 - [ ( 2,4 - di fluorobenzyl ) oxy] - 6 -methylpyridin-2 (IH) -one Step I: Preparation of 4-[(2,4-difluorobenzyl)oxy]-l-(2,6difluoro-4-hydroxyphenyl)-6-methylpyridin-2(iH)-one O l 4- [ (2,4-Difluorobenzyl) oxy] -6-methyl-l- (2,4,6trif!uorophenyl)pyridin-2(IH)-one (step 2 above) (i0.0 g, 26.2 mmol) was heated to 45°C with KOSiMe 3 (10.08 g, 78.6 mmol) in 50 ml of tetrahydrofuran for 4 days. The reaction was diluted with 30 ml of ethyl acetate and washed with IN HCI and water, dried over MgSO 4 , and evaporated to give an orange solid. The solid was stirred in hot 60% ethyl acetate/hexanes and filtered to give a white solid, which was dried in vacuo to obtain a white solid (3.79 g, 38%). The filtrate was found to contain a mixture of desired product and the ortho substituted regioisomer. IH NMR (400 MHz, CDC!]) 6 7.42 (app q, J = 7.70 Hz, IH), 6.95 - 6.83 (m, 2H), 6.34 (d, J = 9.40 Hz, 2H), 6.05 (app s, 2H) , 5.06 (s, 2H) , 2.01 (s, 3H) ; LC/MS, tr = 2.80 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C) , ES-MS m/z 380 (M+H). ES-HRMS m/z 380.0926 (M+H calcd for C 19 HI 3 F 4 NO 3 requires 380.0904). Step 2: Preparation of the title compound 4-[(2,4Difluorobenzyl)oxy]-l-(2,6-difluoro-4-hydroxyphenyl)-6methylpyridin-2(iH)-one ( from step i) (3.73 g, 8.14 mmol was stirred as a suspension at room temperature with Nbromosuccinimide (1.52 g, 8.55 mmol) in 30 ml CH 2 C1 2 overnlght. LC-MS showed a 60% starting material. The solid was filtered off, dissolved in 30 ml of CH Cl 2 /N,N-dimethylformamide and stirred with more N-bromosuccinimide (0.76 g, 4.28 mmol) overnight. LC-MS showed the tri-brominated product as the major product. The reaction was poured into water and extracted with n-butanol. The combined organic layers were evaporated on a rotary evaporator and the resulting solid was washed with diethyl ether and dried in vacuo to yield a white solid (873 mg, 17%). IH NMR (400 MHz, CDCI 3 ) 6 7.67 (app q, J = 7.80 Hz, IH), 7.32 (dt, J = 4.86, 2.11 Hz, IH), 7.16 (dr, J = 8.48, 1.84 Hz, IH), 6.79 (s, IH), 5.35 (s, 2H), 2.08 (s, 3H) ; LC/MS, tr = 3.26 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 616 (M+H). ES-HRMS m/z 615.8234 (M.H calcd for C 19 HI 0 Br 3 F 4 NO 3 requires 615.8200). Example 324 oxopyridin1 (2H) -yl ] -3,5-difluorophenoxy} acetamide Step i: Preparation of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l- (2,6-difluoro-4-hydroxyphenyl)-6-methylpyridin-2(iH)-one 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-(2,4,6- trif!uorophenyl)pyridin-2(iH)-one ( above) (7.5 g, 16.3 mmol) was heated to 45°C with KOSiMe (10.08 g, 78.6 mmol) in 50 ml of tetrahydrofuran for 48 hours. The reaction was diluted with 30 ml of ethyl acetate and washed with IN HCI and water, dried over MgS0 4 , and evaporated to give a black oil. The oil was dissolved in ethyl acetate. A precipitate formed upon standing, which was filtered, washed with ethyl acetate and dried in vacuo to obtain a white solid (2.80 g, 37%). The filtrate showed the presence of desired product and the ortho substituted regioisomer. IH NMR (400 MHz, DMSO-d 6 ) 5 7.66 (q, J = 7.92 Hz, IH), 7.32 (dr, J = 8.77, 2.19 Hz, IH), 7.15 (m, IH) , 6.73 (s, IH), 6.67 (d, J = 9.66 Hz, 2H) , 5.33 (s, 2H) , 2.03 (s, 3H) ; LC/MS, tr = 2.92 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 458 (M+H) . ES-H MS m/z 457.9995 (M+H calcd for CIgHI 2 BrF 4 NO 3 requires 458.0009). Step 2: Preparation of the title compound 3-Bromo-4- [(2,4difluorobenzyl)oxy]-l- (2,6-difluoro-4-hydroxyphenyl)-6- eth l i.clin: 2,(IH)-one ( fL m step l) (500 mg, 1_.09 mmQi) was stirred briskly with 2-bromoacetamide (196 mg, 1.43 mmol) and K 2 CO (282 rag, 2.05 mmol) in 5 ml of N,N-dimethylformamide at room temperature for 24 hours. The reaction was poured quickly into cold water and the resulting solid was filtered, washed with water, acetoni rile, and diethyl ether, and dried in vacuo to give a white solid (289 mg, 51%). IH NMR (400 MHz, DMSO-d ) 6 7.66 (q, J = 7.92 Hz, IH), 7.61 (br s, IH), 7.45 (br s, IH), 7.33 (dt, J = 10.07, 2.15 Hz, IH), 7.16 (dt, J = 8.53, 1.88 Hz, 1H), 6.99 (d, J = 9.54 Hz, 2H), 6.76 (s, IH), 5.34 (s, 2H) , 2.03 (s, 3H) ; LC/MS, t= = 2.70 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 515 (M+H). ES-HRMS m/z 515.0245 (M+H calcd for C 2 HIsBrF 4 N 2 0 4 requires 515.0224). Example 325 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -i- [2,6-difluoro-4- (2hydroxyethoxy) phenyl ] - 6 -methylpyridin2 (IH) -one The title compound was prepared by a procedure similar to the one described for Example 324 . IH NMR (400 MHz, DMSO-d 6 ) 6 7.66 (q, J = 7.92 Hz, IH) , 7.33 (dt, J = i0.04, 2.19 Hz, IM), 7.17 (dr, J = 8.68, 1.84 Hz, IH), 6.99 (d, J = 9.67 Hz, 2H), 6.75 (s, IH) , 5.34 (s, 2H) , 4.92 (t, J = 4.86 Hz, IH) , 4.07' (t, J = 4.77 Hz, 2H), 3.70 (t, J = 4.83 Hz, 2H), 2.03 (s, 3H); LC/MS, tr = 2.81 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min, at 254 nm, at 50°C), ES.-MS m/z 502 (M+H). ES-HRMS m/z 502.0291(M+H calcd for C 21 HI 6 BrF 4 N0 4 requires 502.0272). Example 326 F 3-bromo-l-(2,6-difluorophenyl)-4-{[4-fluoro-2- (hydroxymethyl)benzyl]oxy}-6-methylpyridin-2(1H)-one Step i: Preparation of l-(2,6-difluorophenyl)-4-{[4-f!uoro-2- (hydrox3nnethyl)benzyl]oxy}-6-methylpyridin-2(IH)-one F\ F l-(2,6-Difluorophenyl)-4-hydroxy-6-methylpyridin-2(IH)-one (step I) (3.0 g, 12.65 mmol) was dissolved in N,N- dimethylformamide and cooled to 0°C. Triphenylphosphine (3.98 g, 15.18 mmol) and diethyl azodicarboxylate (2.39 ml, 15.18 mmol) were added and stirred for I0 minutes. 1,2Bis(hydroxymethyl)-4-fluorobenzene (2.57 g, 16.44 mmol) was added and stirred at 0°C for 1 hour, then allowed to warm to room temperature and stirred overnight. LC-MS showed only 1 product, not a mixture of regioisomers, as expected. The reaction was added to water and extracted 3 times with ethyl acetate. The combined organic layers were dried over MgSO 4 and evaporated. A Biotage silica column was done using 60% ethyl acetate/hexanes as an eluent. Desired product, with a substantial impurity was obtained. Another Biotage silica column was ran using 30% ethyl acetate/hexanes to obtain pure product. The resulting oil was triturated with diethyl ether to obtain a white solid (720 rag, 15%). H NMR (300 MHz, CITED) 6 7.51 - 7.39 (m, 2H) , 7.26 (dd, J = 9.62, 2.51 Hz, IH) , 7.13 - 7.01 (m, 3H) , 6.03 (d, J = 2.42 Hz, IH), 5.96 (d, J = 2.41 Hz, IH), 5.06 (s, 2H), 4.73 (s, 2H), 2.81 (br s, IH), 2.02 (s, 3H) ; LC/MS, tr = 2.37 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min, at 254 nm, at 50°C) , ES-MS m/z 376 (M+H) . ES-HR/MS m/z 376. 1181 (M+H calcd for Cz 0 H GF 3 N0 3 requires 376.1155) . Identity of the positional isomer was determined from hmbc, 2-D NMR experiments using H to C 2and 3bond coupling. Step 2: Preparation of the title compound 1-(2,6Difluorophenyl)-4-{[4-fluoro-2-(hydroxymethyl)benzyl]oxy}-6methylpyridin-2(iH)-one ( from step I) (350 mg, 0.93 mmol) was stirred at room temperature with N-bromosuccinimide (199 mg, 1.12 mmol) in 1.5 ml CH 2 CI for 1.5 hours. The reaction was evaporated on a rotary evaporator and the resulting solid was washed 4 times with acetonitrile and dried in vacuo to yield a white solid (197 mg, 47%). H NMR (300 MHz, CDCI 3 ) 6 7.53 - 7.43 (m, 2H), 7.25 (dd, J = 9.46, 2.62 Hz, IH), 7.11 - 7.03 (m, 3H), 6.25 (s, IH), 5.31 (s, 2H) t 4.81 (s, 2H), 2.28 (br s, IH), 2.10 (s, 3H) ; LC/MS, tr = 2.38 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 454 (M+H) . ES-HRMS m/z 454.0247 (M+H calcd for C 20 HIsBrF 3 NO 3 requires 454.0260). Example 327 (hydroxymethyl) benzyl ] oxy} - 6 -methylpyridin2 (IH) -one i- (2,6-Difluorophenyl) -4-{ [4-fluoro-2- (hydroxymethyl) benzyl ] oxy}- 6-methylpyridin-2 (IH) -one (step 1 above) (275 mg, 0.73 mmol) was stirred at reflux with Nchlorosuccinimide (117 mg, 0.88 mmol) and dichloroacetic acid (0.03 ml, 0.36 mmol) in 1.5 ml CH 2 C1 2 overnight. The reaction was evaporated on a rotary evaporator and the resulting solid was washed 4 times with ethyl acetate and with diethyl ether and dried in vacuo to obtain a white solid (65.5 rag, 22%). IH N-MR (300 MHz, CDCI 3 ) 6 7.527.43 (m, 2H), 7.26 (dd, J = 9.38, 2.52 Hz, IH) , 7.12 - 7.04 (m, 3H) , 6.27 (s, IH) , 5.32 (s, 2H) , 4.82 (s, 2H) , 2.29 (br s, IH) , 2.11 (s 0 3H) ; LC/MS, tr = 2.32 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 rim, at 50°C), ES-MS m/z 410 (M+H). ES-HRMS m/z 410.0755 (M+H calcd for C 20 HIsCIF 3 NO requires 410.0765). Example 328 O O 3- [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-2-methyl-N2-morpholin-4-ylethyl)benzamide Step I: Preparation of methyl 3-(4-hydroxy-6-methyl-2oxopyridin-l(2H)-yl)-2-methylbenzoate 4-Hydroxy-6-methyl-2-pyrone (72.6 g, 576 mmol) and methyi-3amino-2-methylbenzoate (i00 g, 605 mmol) were suspended in ml of 1,2-dichlorobenzene in a 500 ml, 3-necked round bottom flask equipped with a J-Kem temperature controller probe, a Dean-Stark trap, and a heating mantle. The reaction was heated to 165°C for 15 minutes, during which, water and some 1,2-dichlorobenzene was collected in the Dean-Stark trap. The reaction was allowed to cool to about 80°C. The flask was placed in an ice bath and about 300 ml of toluene was added and stirred. After about 30 minutes, a precipitate formed. The precipitate was filtered and washed 3 times with toluene, 3 times with hot water to remove excess pyrone, and dried in vacuo to give a tan solid (44.6 g, 28% yield), iH NMR (400 MHz, DMSO-d 6 ) 6 10.66 (br s, IH), 7.80 (dd, J = 7.72, 1.28 Hz, IH), 7.33 (dd, J = 7.78, 1.34 Hz, IH), 5.91 (dd, J = 2.41, 0.69 Hz, IH), 5.55 (d, J = 2.42 Hz, IH), 3.82 (s, 3H), 2.06 (s, 3H), 1.73 (s, 3H) ; LC/MS, tr = 1.85 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 274 (M+H). ES-HRMS m/z 274.1078 (M+H calcd for CI HIsNO 4 requires 274.1074). Step 2: Preparation of methyl 3-[4-[(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]-2-methylbenzoate methylbenzoate ( fl-om Step i) (42.0 g, 154 mmol) was stirred briskly at room temperature with 2,4-difiuorobenzyl bromide (19.7 ml, 154 mmol) and K 2 CO 3 (31.8 g, 231 retool) in 250 ml of N,N-dimethylformamide. After stirring overnight, the reaction was poured into 1 L of cold water. The solution was extracted 3 times with ethyl acetate and the organic layers were dried over MgSO 4 , and evaporated. The product was carried on to the next step as a crude oil (60.4 g, 85%) . IH NMR (400 MHz, CDCI 3) 6 7.96 (dd, J = 7.85, 1.28 Hz, IH), 7.45 - 7.34 (m, 2H), 7.27 - 7.23 (m, IH) , 6.94 - 6.84 (m, 2H) , 5.98 (d, J = 2.68 Hz, IH) , 5.92 (dd, J = 2.69, 0.81 Hz, IH) , 5.01 (s, 2H) , 3.88 (s, 3H) , 2.28 (s, 3H) , 1.81 (s, 3H) ; LC/MS, tr = 2.96 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 400 (M+H). ES-HRMS m/z 400.1341 (M+H calcd for CnHIgF 2 NO 4 requires 400.1355). Step 3: Preparation of 3-[4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]-2-methylbenzoic acid O O Methyl 3-[4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-2-methylbenzoate ( from Step 2) (60.0 mg, 150 mmol) was stirred with 2.5 N NaOH (120 ml, 300 mmol) in 375 ml of tetrahydrofuran and 75 ml of water at room temperature overnight. The reaction was acidified with 1 N HCI, 350 ml of water was added and the solution was extracted 3 times with ethyl acetate. The comb ned organic layers were dried over MgS0 4, filtered and evaporated. The resulting solid was filtered, washed with ethyl acetate and dried in vacuo to yield a white solid 33.8 g, 58%). IH NMR (400 MHz, CDCI 3 ) 6 7.98 (dd, J = 7.92, 1.20 Hz, IH), 7.43 (app q, J = 7.70 Hz, IH) , 7.38 (t, J = 7.72 Hz, IH), 7.35 (dd, J = 7.81, 1.21 Hz, IH) , 6.92 - 6.84 (m, 2H), 6.17 (d, J = 2.56 Hz, IH), 6.00 (dd, J = 2.55, 0.81 Hz, IH) , 5.05 (s, 2H) , 2.30 (s, 3H), 1.84 (s, 3H) ; LC/MS, tr = 2.61 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min, at 254 nm, at 50°C) , ES-MS m/z 386 (M+H) . ES-HR/MS m/z 386. 1228 (M÷H calcd for CnHI F 2 NO 4 requires 386.1198) . Step 4: Preparation of 3-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-2methylbenzoic acid . 3-[4-[(2,4-Difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]-2-methylbenzoic acid ( from Step 3) (23.0 g, 59.7 mmol) was stirred at room temperature with N-bromosuccinimide (12.74 g, 71.6 mmol) in 120 ml of CH 2 C1 2 for 2 hours. The reaction was evaporated on a rotary evaporator and the resulting solid was stirred in acetonitrile for 1 hour, washed 7 times with acetonitrile and dried in vacuo to yield a white solid (19.14 LC/MS, tr = 2.69 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 464 (M+H) . ES-H MS m/z 464.0284 (M+H calcd for CnHI 6 BrF 2 N0 4 requires 464.0304). Step 5: Preparation of the title compound 3-[3-Bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-2methylbenzoic acid ( from Step 4 above) (500 mg, 1.08 mmol) was dissolved in 5 ml of CH 2 C1 2 . 4-(2-Aminoethyl)morpholine (170 i, 1.29 mmol) was added, followed, in order, by EDCI (247 mg, 1.29 mmol), l-hydroxybenzotriazole (174 mg, 1.29 mmol) and triethylamine (301 i, 2.16 mmol). The reaction was stirred at room temperature overnight. The reaction was quenched with NH 4 CI and extracted 3 times with ethyl acetate. The combined organic layer was dried over MgSO 4 and evaporated. The resulting oil was Eriturated with diethyl ether/hexane to obtain a solid, which was dried in vacuo to give a white solid (472 mg, 76%). IH NMR (400 MHz, DMSO-d ) 6 7.64 (app q, J = 7.79 Hz, IH), 7.47 (dd, J = 7.65, 1.01 Hz, IH), 7.39 (t, J = 7.75 Hz, IH), 7.17 (dd, J = 7.65, 0.81 Hz, IH), 7.01 (dt, J = 8.26, 1.61 Hz, IH), 6.91 (dt, J = 9.42, 2.32 Hz, IH), 6.49 (t, J = 5.04 Hz, IH) , 6.18 (s, IH) , 5.30 (s, 2H) , 3.73 (t, J = 4.53 Hz, 4H), 3.68 - 3.47 (m, 2H), 2.59 (t, J = 5.94 Hz, 2H), 2.51 (t, J = 4.33 Hz, 4H), 2.15 (s, 3H), 1.98 (s, 3H) ; LC/MS, tr = 2.27 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 576 (M+H) . ES-HRMS m/z 576.1313 (M+H calcd for C 2 vH 28 BrF 2 N 3 0 4 requires 576.1304). Examples 329-337 The following compounds are prepared essentially according to the procedure set forth for Example 328: Example M+H ESHRMS No. R MF Requires m/z Ex. 329 -N-HCH 2 CH 2 OCH 3 C 24 HnBrF 2 N 2 0 4 521.0882 521.0906 Ex. 330 -N (CH 3 ) 2 C 2 H 20 BrF 2 N 2 0 3 491.0776491.0752 Ex. 331 -NHCH 2 CH 2 OH C 23 H= 0 BrFHN 2 0 4 507.0726 507.0689 Ex. 332 - N-HCH 3 C 22 HIsBrF 2 N 2 0 3 477.0620477.0585 Ex. 333 -N (CH 3 ) CH 2 CH 2 OH C 24 H 22 BrF 2 N O 4 521.0882 521.0890 Ex. 334 4methylpiperazin1 -yl C 26 H 2 sBrF 2 N 3 0 3 546.1198 546.1187 Ex. 335 morpholin-4 -yl C 2 sH 22 BrF 2 N 2 0 4 533.0882 533.0856 Ex. 336 -N (CH 3 ) CH 2 CH 2 OCH 3 C 2 sH 24 BrF 2 N 2 0 4 535.1039 535.1055 Ex. 337 -NH 2 C 21 HI 6 BrF 2 N 2 0 3 463.0463 463.0492 NMR characterization of compounds of Examples 329-337 Example NMR Data Example 338 3-bromo-4-[(2,4-difluor 0 benzyl) 0 xy]-l-[3-(hydr 0 xymethyl)_ 2_ methylphenyl]-6-methylpyridin-2(iH)-one 3-[3-Bromo-4-[(2,4-diflu 0 r 0 benzyl) 0 xy]-6-methyl2- 0 x 0 pyridin_ l(2H)-yl]-2-methylbenzoic acid (Step 4 above) (2.0 g, 4.31 mmol) was cooled to 0°C in I0 ml of tetrahydrofuran. 19.5 ml of IM BH3THF in tetrahydrofuran was added and stirred overnight, allowing the temperature to rise to room temperature. The reaction was cooled back down to 0°C and ice chips were added to quench the reaction. The slurry was extracted 3 times with an ethyl acetate/tetrahydrofuran mixture. The combined organic layers were washed with brine, dried over MgSO 4 , filtered and evaporated to give a white solid (1.73 g, 89%). IH N-MR (400 MHz, DMSO-d ) 6 7.67 (app q, J = 7.92 Hz, IH), 7.46 (d, J = 7.52 Hz, IH), 7.32 (dt, J = 10.74, 2.42 Hz, IH) , 7.30 (t, J = 7.72 Hz, iH) , 7.17 (dt, J = 8.46, 1.88 Hz, IH), 7.03 (d, J = 7.38 Hz, IH), 6.68 (s 0 IH), 5.32 (s, 2H), 4.51 (s, 2H), 3.29 (d, J = 9.40 Hz, IH), 1.85 (s, 3H) , 1.81 (s, 3H) , LC/MS, tr = 2.64 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 450 (M+H) . ES-HRMS m/z 450.0480 (M+H calcd for C 21 HIsBrF 2 NO] requires 450.0511) . Example 339 3-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-N-(2-methoxyethyl)-2-methylbenzamide Step i: Preparation of 3-[3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-2methylbenzoic acid yl]-2-methylbenzoic acid (Step 3 above) (i0.0 g, 25.9 mmol) was refluxed with N-chlorosuccinimide (4.15 g, 31.1 mmol) and dichloroacetic acid (1.06 ml, 12.9 mmol) in 50 ml of CH 2 C1 2 overnight. The reaction was evaporated on a rotary evaporator and the resulting solid was stirred in acetonitrile for minutes, washed 4 times with acetonitrile and dried in vacuo to yield a white solid (8.3 g, 78%). IH NMR (300 MHz, DMSO-d 6 ) 6 7.93 (dd, J = 7.15, 1.92 Hz, IH), 7.72 (app q, J = 7.92 Hz, IH), 7.52 - 7.35 (m, 3H), 7.22 (dr, J = 8.47, 2.01 Hz, IH), 6.80 (s, IH), 5.38 (s, 2H), 2.14 (s, 3H), 1.93 (s, 3H) ; LC/MS, tr = 2.64 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 420 (M+H). ES-HRMS m/z 420.0806 (M+H calcd for CnHI CIF 2 N0 4 requires 420.0809)° Step 5: Preparation of the title compound 3- [3-Chloro-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-2methylbenzoic acid ( from Step 1 above) (500 mg, 1.19 mmol) was dissolved in 5 ml of CH 2 C1 2 . 2-Methoxyethylamine (129 pl, 1.49 mmol) was added, followed, in order, by EDCI (286 mg, 1.49 mmol), l-hydroxybenzotriazole (202 mg, 1.49 mmol) and triethylamine (332 #i, 2.38 mmol). The reaction was stirred at room temperature overnight. The reaction was quenched with NH 4 C1 and extracted 3 times with ethyl acetate. The combined organic layer was dried over MgSO 4 and evaporated. The resulting solid was dried in vacuo to give a white solid (401 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 477 (M+H). ES-HRMS m/z 477.1363 (M+H calcd for C 24 H 23 CIF 2 N 2 0 4 requires 477.1387). Example 340 O O 3-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-N,2-dimethylbenzamide The title compound was prepared by a procedure similar to the one described for Example 337, where methylamine was used as the amine and the product was obtained in 73% yield, i}{ NMR (300 MHz, DMSO-d ) 6 8.37 (app d, J = 4.64 Hz, IH), 7.72 (app q, J = 7.92 Hz, IH), 7.44 - 7.35 (m, 4H), 7.22 (dt, J = 8.54, 1.61 Hz, IH) , 6.78 (s, IH) , 5.37 (s, 2H) , 2.79 (d, J = 4.43 Hz, 3H) , 1.95 (s, 3H) , 1.94 (s, 3H) ; LC/MS, tr = 2.46 minutes (5 to 95% acetonitrile/wa er over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 433 (M+H) . ES-HRMS m/z 433.1163 (M+H calcd for C 22 HIgCIF 2 N 2 0 3 requires 433.1125). Example 341 3_ [ 3 _ch 10 r 0 - 4 -[(2,4-diflu 0 r 0 benzyl)oxy]-6-methyl-2-oxopyridin1(2H)_yl]_N-(2-hydroxyethyl)-2-methylbenzamide The title compound was prepared by a procedure similar to the one described for , where ethanolamine was used as the amine and the product was obtained in 65% yield. IH NMR (400 MHz, DMSO-d 6) 6 8.39 (t, J = 5.51 Hz, IH), 7.67 (app q, J = 7.88 Hz, IH), 7.43 - 7.33 (m, 3H), 7.23 (d, J = 7.25 Hz, IH), 7.17 (dt, J = 8.39, 1.66 Hz, IH), 6.74 (s, IH), 5.32 (s, 2H), 3.48 (br s, 2H), 3.31 - 3.26 (m, 2H), 1.90 (s, 3H), 1.89 (s, 3H) ; LC/MS, tr = 2.34 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 463 (M+H) . ES-HRMS m/z 463.1220 (M+H calcd for C 23 H 21 CIF 2 N 2 0 4 requires 463.1231). Example 342 3- [3-chloro-4- [(2,4-difluorobenzyl)oxy] -6-methyl-2-oxopyridini (2H) -yl] -2-methylbenzamide 3- [3-Chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyi-2-oxopyridin1 (2H)-yI] -2-methylbenzoic acid (Step 1 above) (500 mg, 1.19 mmol) was stirred with 2-chloro-4,6-dimethoxy-l,3,5-triazine (251 rag, 1.43 retool) and N-methylmorpholine (392 i, 3.57 retool) in 5 ml of tetrahydrofuran at room temperature for 2 hours. 2.5 ml of NH 4 0H was added and stirred at room temperature for 2.5 hours. The reaction was diluted with tetrahydrofuran and ethyl acetate and extracted. The combined organic layers were washed with NaHC0 3 , 1 N HCI, and brine, dried over MgS0 4 , filtered and evaporated. The resulting solid was dried in vacuo to obtain a white solid (313 rag, 63%). IH NMR (400 MHz, DMSO-d ) 7.87 (br s, IH), 7.66 (q, J = 7.83 Hz, IH), 7.48 - 7.30 (m, 3H), 7.23 (d, J = 7.52 Hz, IH), 7.17 (t, J = 7.65 Hz, IH) , 6.73 (s, IH), 5.32 (s, 2H) , 1.94 (s, 3H), 1.88 (s, 3H) ; LC/MS, tr = 2.44 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 419 (M+H). ESHRMS m/z 419. 0963 (M+H calcd for C 21 HIvCIF 2 N 2 0 3 requires 419.0969). Example 343 F 0 F,.-x, _/ CN 4- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] - 2-oxopyridin1 (2H) - yl] -3,5-difluorobenzonitrile Step 1 : Preparation of 4-[(2,4-difluorobenzyl)oxy]pyridine Iox i de 2, 4-difluorobenzyl alcohol (i00. g, 0.694 mol) and 4nitropyridine N-oxide (98. g, 0.700 mol)are combined with 250 g Cs 2 CO 3 (i.i eq) in 2.5 L anhydrous dimethylformamide and heated to 80°C with stirring. The reaction was followed by 19F-NMR (crude reaction mixture with external D 2 0 reference) and complete after 40 h. The mixture was filtered hot; product crystallized out on cooling. 90.21 g (55%) of white plates were collected by filtration and washed with diethyl ether. The mother liquor was diluted with 2.5 L diethyl ether and stored in the freezer overnight, yielding a second crop 68.76 g (41%, combined yield 96%). IH-NMR (400 MHz, DMSO-d 6 ) 6 8.06 (m, 2 H), 7.61 (quartet, J = 8.45 Hz, IH), 7.30 (t, J = 10.37 Hz,IH), 7.12, (t, J = 8.45 Hz, IH), 7.09 (d, J = 5.06 Hz, 2H), 5.14 (s, 2H). 19F-NMR (400 MHz, DMSO-d 6 ) 6-109.43 (quintet, J = 7.78 Hz, IF), -113.82 (quartet, J = 9.55 Hz, IF). LC/MS tr = 3.90 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 238 (M+H) . Step 2: Preparation of 4-[(2,4-difluorobenzyl)oxy]-pyridin4-[(2,4-difluorobenzyl)oxy]pyridine 1-oxide ( from Step I) (30.0 g , 0.127 mol), anhydrous potassium acetate (25 g, 0.25 mol), acetic anydride (25 g, 0.25 mol), and l0 ml acetic acid were combined in a 250-mi round-bottomed flask with overhead stirring and heated to 130°C for 4 hours. The mixture was concentrated under vacuum, the solids dissolved in 95 ml acetonitrile: 5 ml water, filtered through charcoal and poured into 600 ml ice with stirring. The mixture was allowed to stand overnight at room temperature, then 9.62 g (30%) product collected by filtration as a medium brown solid (adequate for the next step without purification). IH-NMR (400 M!4z, DMSO-d 6 ) 6 ii.i0 (s, IH), 7.59 (quartet, J = 9.91 Hz, IH), 7.29 (t, J = 10.36 Hz, IH), 7.21 (d, J = 8.20 Hz, IH), 7.11 (t, J = 8.48 Hz, IH), 5.83 (m, 2H), 5.02 (s, 2H). 19F-NMR (400 MHz, DMSOd 6) 6 -109.57(quintet, J = 7.66 Hz, IF) -113.88 (quartet, J = 8.93 Hz, IF) . LC/MS tr = 4.29 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 254 nm, at 50°C) ES-MS m/z 238 (M+H) . Step 3: Preparation of 3-chloro-4-[(2,4difluorobenzyl)oxy]pyridin-2(iH)-one 4- [(2,4-difluorobenzyl)oxy]-pyridin-2(IH)-one ( from Step 2) (8.60 g, 36.3 mmol) was stirred in 150 ml dimethylformamide and treated with N-chlorosuccinimide (5.4 g, 39.9 mmol) . After 15 hours, the precipitate was collected by filtration (5.11 g, 52%) yeilding a lustrous white solid. The mother liquor was diluted to 500 ml with diethyl ether, providing 2.47 g (25%) in a second crop. H-NMR (400 MHz, DMSO-d 6 ) 6 11.87 (s, IH), 7.60 (quartet, J = 6.34 Hz, IH), 7.43 (d, J = 7.58 Hz, IH), 7.31 (dt, J = 10.08, 2.21 Hz, IH), 7.14 (dr, J = 8.65, 1.79 Hz, IH), 6.44 (d, J = 7.49 Hz, IH), 5.28 (s, IH) . 19F-NMR (400 MHz, DMSO-d ) 6 -109.58 (quintet, J = 7.75 Hz, IF) , -113.68 quartet, J = 8.68 Hz, IF). LC/MS tr = 4.47 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 254 nm, at 50°C) ES-MS m/z 272, 274 3:1 (M+H) . Step 4: Preparation of the title compound 3-chloro-4- [ (2,4-difluorobenzyl) oxy] pyridin-2 (IH) -one ( from step 3) (3.25 g, 11.9 mmol) was combined with Cs 2 COa (3.93 g, 12.1 mmol) in 50 ml dimethylformamide and heated to 70°C, stirring under nitrogen. 3,4,5-trifluorobenzonitri!e (1.83 g, 11.9 mmol ) was added. After 4 hours, the mixture was filtered, concentrated in vacuo, washed thrice with hot cyclohexane, dissolved in tetrahydrofuran, treated with MgSO 4 and charcoal, and filtered. The solution was evaporated leaving a fine white solid (3.99 g, 82%). IH-NMR (400 MHz, DMSO-d 6) 6 8.12 (d, J = 7.59 Hz, 2H) , 7.92 (d, J = 8.31 Hz, IH) , 7.65 (quartet, J = 6.77, IH) , 7.34 (dt, J = 9.81, 2.71 Hz, IH), 7.16 (dr, J = 8.59, 2.50 Hz, IH), 6.87 (d, J = 8.01 Hz, IH) , 5.39 (s, 2H) . 19F-NMR (400 MHz, DMSO-d 6 ) 6 -109.17 (quintet, J = 8.97 Hz, IF), -ll3.51(quartet, J = 9.53 Hz, iF), ALIBI (d, J = 7.69 Hz, 2F) . LC/MS tr = 5.51 minutes (095% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 409 (M+H). ES-HRMS m/z 409.0351 (M+H calcd for C gHI 0 CIF 4 N 2 0 2 requires 409.0361). Example 344 0 F NH2.HCI l-[4-(aminomethyl)-2,6-difluorophenyl]-3-chloro-4-[(2,4difluorobenzyl)oxy]pyridin-2(iH)-one hydrochloride Step I: Preparation of tert-butyl 4-[3-chloro-4- [(2,4difluorobenzyl)oxy]-2-oxopyridin-i(2H)-yl]-3,5difluorobenzylcarbamate H O F 4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-2-oxopyridin-l(2H)- yl]~3,5-difluorobenzonitrile (2.84 g, 6.95 mmol), di-t-butyldicarbonate (3.18 g, 14.6 mmo!), and nickel(II) chloride (0.90 g, 6.95 mmol) were combined with 40 ml methanol and ml tetrahydrofurar and cooled to 0°C stirring in an ice bath. portions over i0 minutes to control foaming, and the reaction was stirred 1 hour. Additional sodium borohydride (0.50 g, 13.2 mmol) was required to force the reaction to completion by LC. A color change from yellow to black persisted on completion. The mixture was filtered through a bed of charcoal layered on anhydrous MgS0 4 and evaporated to dryness. Excess di-t-butyl-dicarbonate and byproduct t-butanol were removed by repeated heating with water to 80°C in vacuo, giving the product as a fine white powder (3.11 g, 87%). IH- N-MR (400 MHz, DMSO-d ) 6 7.89 (d, J = 8.04 Hz, IH), 7.65 (quartet, J = 6.73 Hz, IH), 7.55 (t, J = 6.73 Hz,IH), 7.34, (dt, J = 10.05, 2.51 Hz, IH), 7.16 (m, 3H), 6.77 (d, J = 8.18 Hz, IH) , 5.34 (s, 2H) , 4.18 (d, J = 5.68 Hz, 2H), 1.34 (s, 9H) . ZgF-NMR (400 MHz, DMSO- ) 6 -109.26 (quintet, J = 6.91 Hz, IF) , -113.53 (quartet, J = 7.73 Hz, IF), -120.32 (d, J = 8.91 Hz, 2F) . LC/MS tr = 5.90 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 513 (M+H) . ES-HRMS m/z 513.1164 (M+H calcd for C 24 H 22 CIF 4 N 2 0 4 requires 513.1199). Step 2: Preparation of the title compound . tert-butyl 4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-2oxopyridin-l(2H)-yl]-3,5-difluorobenzylcarbamate ( from step 3) (1.39 g, 2.71 mmol) was dissolved in 20 ml tetrahydrofuran and treated with 4 ml concentrated hydrochloric acid. The solution was evaporated and dried in vacuo to a fine white solid (1.20 g, 99%). IH-NMR (400 MHz, DMSO-d ) 6 8.54 (m, 2H), 7.86 (d, J = 7.57 Hz, IH), 7.65 (quartet, J = 7.62, IH), 2F) . LC/MS tr = 4.33 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 413 (M+H). ES-HRMS m/z 413.0712 (M+H calcd for C 19 HI 4 CIF 4 N 2 0 2 requires 413.0674). Example 345 I 0 .NH.HCl F 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-{2,6-difluoro-4- [(methylamino)methyl]phenyl}pyridin-2(IH)-one hydrochloride Step i: Preparation of tert-butyl 4- [3-chloro-4- [(2,4difluorobenzyl)oxy]-2-oxopyridin-l(2H)-yl]-3,5difluorobenzyl(methyl)carbamate I O tert-butyl 4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-2oxopyridin-l(2H)-yl]-3,5-difluorobenzylcarbamate ( from Step i) (252 mg, 0.491 mmol) and iodomethane (75 mg, 0.528 mmol) are combined in 8 ml anhydrous dimethylformamide. Sodium hydride 60% in minera! oil (30 mg, 0.75 mmol) was added and the mixture stirred under nitrogen at room temperaure for 1 hour. Saturated aqueous NH 4 CI was added (4 ml) followed by ml water and the product was extracted into ethyl acetate, washed with brine, dried over MgSO 4 , filtered, and evaporated to give the product as a white powder (208 mg, 80%). IH-NMR (400 MHz, DMSO-d ) 6 7.87 (d, J = 7.85 Hz, IH) , 7.64 (quartet, J = 6.66 Hz, IH), 7.32, (dt, J = 9.39, 3.29 Hz, IH), 7.13 (m, 3H), 6.77 (d, J = 7.94 Hz, i), 5.38 (s, 2H), 4.43 (s, 2H), 2.90 (s, 3H) , 1.40 (br m, 9H) . 19F-NMR (400 MHz, DMSO-d 6 ) 6 - 109.25 (quintet, J = 8.93 Hz, IF), -113.53 (quartet, J = 9.73 Hz, IF), -i19.89(d, J = 9.35 Hz, 2F). LC/MS tr = 6.16 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes, then 95% acetonitrile for 2 minutes, at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 527 (M+H). ES-HRMS m/z 527.1338 (M+H calcd for C 2 sH 24 CIF 4 N 2 0 4 requires 527.1355) . Step 2: Preparation of the title compound tert-butyl 4- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2oxopyridin1 (2H) -yl ] - 3,5-difluorobenzyl (methyl) carbamate ( from step i) (188 mg, 0. 357 mmol) was subjected to the conditions of Step 2, yielding a fine white solid (165 mg, 100%). IH-NMR (400 MHz, DMSO-d 6 ) 6 9.30 (br s, 2H), 7.89 (d, J = 7.99 Hz, IH), 7.65 (quartet, J = 7.64, IH), 7.55 (d, J = 8.66 Hz, 2H) , 7.34 (dt, J = 9.93, 2.57 Hz, IH) , 7.17 (dr, J = 8.49, 2.48 Hz, IH) , 6.81 (d, J = 8.01 Hz, IH) , 5.39 (s, 2H) , 4.21 (s, 2H) , 2.56 (s, 3H) . I F-NMR (400 MHz, DMSO-d 6 ) 6 109.20 (quintet, J = 7.56 Hz, IF) , -113.52 (quartet, J = 9.67 Hz, IF), -119.21 (d, J = 8.79 Hz, 2F) . LC/MS tr = 4.30 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 427 (M+H) . ES-HRMS m/z 427. 0816 (M+H calcd for C 20 HI 6 CIF 4 N 2 0 requires 427.0831) . Example 346 0 ,NH.HCI F 3-chloro-l- (4- { [ (cyclopropylmethyl) amino] methyl} -2,6difluorophenyl) -4- [ (2,4-difluorobenzyl) oxy] pyridin-2 (IH) hydrochloride The title compound was prepared by direct analogy with replacing iodomethane with bromocyclopropylmethane extending the reaction time to 6 hours in Step I. Step i: F O 1 tert-butyl 4- [3-chloro-4- [(2,4-difluorobenzyl)oxy]-2oxopyridin1 (2H) -yl] -3,5difluorobenzyl (cyclopropylmethyl) carbamate IH-NMR (400 MHz, DMSO-d ) 6 7.89 (quartet, J = 6.81 Hz, IH), 7.33, (d, J = 7.91 Hz, IH) (dt, J = 9.90, 2.26 Hz, (quintet, J = 7.77 Hz, IF), -i13.54 (quartet, J = 9.02 Hz, IF), -120.24(m, 2F) . LC/MS tr = 5.99 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes, then 95% acetonitrile for 2 minutes, at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 567 (M+H). ES-HRMS m/z 567.1653 (M÷H calcd for C 28 H 28 CIF 4 N 2 0 4 requires 567.1668). Step 2: Title compound IH-NMR (400 MHz, DMSO-d ) 6 9.51 (br s, 2H), 7.87 (d, J = 7.96 Hz, IH), 7.63 (m, 3H), 7.33 (dt, J = 9.93, 2.65 Hz, IH), 7.16 (dt, J = 8.36, 2.32 Hz, IH), 6.81 (d, J = 7.92 Hz, IH), 5.38 (s, 2H) , 4.22 (br s, 2H) , 2.82 (br s, 2H) , i. I0 (m, IH) , 0.57 (m, 2H), 0.36 (m, 2H) . 19F-NMR (400 M}{z, DMSO-d ) 6 -109.25 (quintet, J = 7.69 Hz, IF) , -113.54 (quartet, J = 9.35 Hz, IF), -120.24 (m, 2F) . LC/MS tr = 4.55 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50oC) ES-MS m/z 467 (M+H). ES-HRMS m/z 467.1119 (M+H calcd for C 23 H 20 CIF 4 N 2 0 2 requires 467.1144). Example 347 0 F L N 4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-2-oxopyridin-l(2H)- yl]-3,5-difluoroN,N-dimethylbenzamide Step i: Preparation of 4-[3-chloro-4-[(2,4difluorobenzyl)oxy]-2-oxopyridin-l(2H)-yl]-3,5difluorobenzamide 4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-2-oxopyridin-l(2H)- yl]-3,5-difluorobenzonitrile (540 mg, 1.32 mmol) and potassium trimethylsilonate 90% (375 mg, 2.63 mmol) are combined in 8 ml anhydrous toluene and heated to reflux with stirring. After I0 minutes, the mixture allowed to cool then partitioned between saturated aqueous ammonium chloride and ethyl acetate. The aqueous layer is extracted twice with ethyl acetate, the combined organics are washed with brine, dried over MgSO 4 , and evaporated in vacuo. The crude product is taken up in tetrahydrofuran and filtered through charcoal layered over silica gel, and the solution evaporated in vacuo to give the product as a white powder (468 mg, 83%). IH-NMR (400 MHz, DMSO-d 6 ) 6 8.22 (br s, 2H), 7.92 (d, J = 7.84 Hz, IH), 7.78 (d, J = 8.45, 2H), 7.65 (quartet, J = 8.40 Hz, IH), 7.34, (dr, J = 10.09, 2.58 Hz, IH), 7.17 (dt, J = 8.72, 2.30 Hz, IH), 6.83 (d, J = 7.91 Hz, IH), 5.39 (s, 2H) . 19F-NMR (400 MHz, DMSO-d ) 6 -109.21 (quintet, J = 7.43 Hz, IF), -113.52 (quartet, J = 9.62 Hz, IF), -118.74 (d, J = 8.88 Hz, 2F). LC/MS tr = 4.67 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes, then 95% acetonitrile ES-MS m/z 427 (M+H) . ES-HRMS m/z 427. 0454 (M+H calcd for C 19 HI 2 CIF 4 N 2 0 requires 427.0467). Step 2: Preparation of the title compound 4- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyrldin-i (2H) - yl]-3,5-difluorobenzamide ( from step i) (243 rag, 0.357 retool) was subjected to the conditions of Step i, with the exception that two equivalents of sodium hydride 60% in mineral oil and iodomethane were used instead of one (46 mg, 0.69 mmol and 103 mg, 0.724 mmol respectively) . IH-NMR (400 MHz, DMSO-dG) 6 7.92 (d, J = 7.76 Hz, IH), 7.66 (quartet, J = 7.33, IH), 7.44 (d, J = 7.59 Hz, 2H), 7.34 (dt, J = 9.88, 2.63 Hz, IH), 7.17 (dt, J = 8.35, 2.06 Hz, IH), 6.83 (d, J = 7.55 Hz, IH), 5.39 (s, 2H) , 2.98 (s, 3H) , 2.91 (s, 3H) . 19F-NMR (400 MHz, DMSOd 6) 6 -109.22 (quintet, J = 8.10 Hz, IF), -l13.53(quartet, J = 9.18 Hz, IF), -118.88 (d, J = 7.77 Hz, 2F). LC/MS tr = 5.13 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50oC) ES-MS m/z 455 (M+H) . ES-HRMS m/z 455.0791 (M+H calcd for C 21 HI 6 CIF 4 N 2 0 3 requires 455.0780). Example 348 I 4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-2-oxopyridin_l(2H)_ yl]-3-fluoro-5me thoxybenzoni rile; Step i: Preparation of 4-[3-chloro-4-[(2,4difluorobenzyl)oxy]-2-oxopyridin-l(2H)-yl]-3-fluoro-5hydroxybenzonitrile F F 4- [3-chloro-4-[(2,4-difluorobenzyl)oxy]-2-oxopyridin-l(2H)- yl]-3,5-difluorobenzonitrile (522 mg, 1.28 mmol) and potassium trimethylsilonate 90% (655 mg, 4.60 mmo!) are combined in 8 ml anhydrous tetrahydrofuran and stirred under nitrogen at room temperature for 2 hours. The precipitated potassium salt of was collected by filtration, washed with a minimum of tetrahydofuran, and dried in vacuo. A portion of this salt (275 mg, 0.618 mmol) was dissolved in 5 ml water, the pH was adjusted below 6 with concentrated hydrochloric acid, the product collected by filtration, washed with water, sucked dry under a blanket of dry nitrogen, and dried further in vacuo overnight (251 mg, 100%, 98% overall). IH-NMR (400 MHz, DMSO-d ) 6 11.46 (br s, IH), 7.74 (d, J = 7.81 Hz, IH), 7.67 (quartet, J = 6.76 Hz, IH), 7.52 (d, J = 8.76, IH), 7.364, (dt, J = 10.18, 2.37 Hz, IH), 7.24 (br s, IH), 7.17 (br t, J = 8.75, IH), 6.74 (d, J = 8.04 Hz, IH), 5.39 (s, 2H) . 19F-NMR (400 MHz, DMSO-d 6 ) 6 -109.26 (quintet, J = 8.50 Hz, IF), -113.52 (quartet, J = 9.29 Hz, IF), -118.06 (d, J = 9.38 Hz, IF). LC/MS tr = 5.13 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes, then 95% acetonitrile for 2 minutes, at 1 ml/min with detection at 215 nm, at 5 °'C) ES-MS m/z 407 (M+H) . ES-P-JAMS m/z 407. 0381 (M.H calcd for CzgHnCIF N 2 0 3 requires 407.0405). Step 2: Preparation of the title compound The potassium salt of 4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]- 2-oxopyridin-l(2H)-yl]-3-fluoro-5-hydroxybenzonitrile ( from Step I) (273 mg, 0.614 mmol) was stirred in 5 ml anhydrous dimethylformamide under nitrogen. Iodomethane (93 mg, 0.66 mmol) was added, and stirring continued for 2 hr. The mixture was diluted to 50 ml with ice-cold water, and the white precipitate collected by filtration. The precipitate was washed thrice with water, sucked dry under a blanket of nitrogen, and dried further in vacuo overnight (242 mg, 87%). IH-NMR (400 MHz, DMSO- ) 6 7.73 (m, 2H) , 7.65 (m, 2H) , 7.34 (dt, J = 9.90, 2.39 Hz, IH), 7.17 (dt, J = 8.75, 2.47 Hz, IH), 6.75 (d, J = 7.97 Hz, IH), 5.37 (s, 2H) , 3.84 (s, 3H) . 19F-NMR (400 MHz, DMSO- ) 6 -109.24 (quintet, J = 7.85 Hz, IF), - l13.54(quartet, J = 9.83 Hz, IF), -118.33 (d, J = 7.77 Hz, IF). LC/MS tr = 5.40 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 421 (M+H). ES-HRMS m/z 421.0522 (M+H calcd for C 20 HI CIF 3 N 2 0 requires 421.0561). Example 349 yl]-3,5-difluorobenzyl}urea Step i: Preparation of the title compound l-[4-(aminomethyl)-2,6-difluorophenyl]-3-chloro-4-[(2,4difluorobenzyl)oxT]pyridin-2(iH)-one hydrochloride (162 mg, 0.361 mmol) is dissolved in 4 ml 50% aqueous acetic acid and treated with potassium cyanate (59 mg, 0.72 mmol). The mixture was stirred 2 hr, then the mixture was diluted to ml with cold water, and the crude product, contaminated with the acetamide, was purified by silica gel chromatography, eluting first with 20% ethanol in hexane then 40% ethanol in hexane. The 50% fractions were pooled by TLC and evaporated, giving the product as a fine white powder (65 mg, 40%). IH-NMR (400 MHz, DMSO- ) 6 7.87 (d, J = 8.07 Hz, IH), 7.64 (quartet, J = 6.53 Hz, IH), 7.33, (dt, J = 9.47, 1.99 Hz, IH), 7.15 (m, 3H) , 6.76 (d, J = 7.97 Hz, IH), 6.59 (m, IH), 5.65 (br s, 2H), 5.38 (s, 2H), 4.22 (m, 2H) . 19F-NMR (400 MHz, DMSO-d 6 ) 6 - 109.22 (quintet, J = 7.86 Hz, IF), -113.51 (quartet, J = 9.40 IF), -120.65 (d, J = 8.75 Hz, 2). LC/MS tr = 4.85 minutes (095% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 456 (M+H). Example 350 l(2H)-yl]-3,5-difluorobenzyl}amino)-l,l-dimethyl-2-oxoethyl acetate Step I: Preparation of the title compound l-[4-(aminomethyl)-2,6-difluorophenyl]-3-chloro-4-[(2,4difluorobenzyl)oxy]pyridin-2(iH)-one hydrochloride (225 mg, 0.501 mmol) is dissolved in a solution of i0 ml tetrahydrofuran and triethylamine (Iii mg, !.i0 mmol) ° 2- acetoxy-2~methyl-propionyl chloride (85 mg, 0.516 mmol) is added, and the mixture stirred for 30 minutes before partitioning between saturated aqueous ammoniom chloride and ethyl acetate. The layers are seperated, and the aqueous phase extracted twice with ethyl acetate. The combined organics are washed with water and brine, then dried over MgS0 4, filtered, and evaporated in vacuo, giving the product as a fine white powder (254 mg, 94%). IH-NMR (400 MHz, DMSOd 6) 6 8.47 (t, J = 6.16 Hz, IH) , 7.88 (d, J = 7.71 Hz, IH), 7.65 (quartet, J = 7.24 Hz, IH), 7.34, (dt, J = 10.04, 2.49 Hz, IH) , 7.16 (m, 3H) , 6.77 (d, J = 7.78 Hz, IH), 5.38 (s, 2H), 4.32 (d, J = 5.93 2H), 2.02 (s, 3H), 1.48(s, 6H) . 19FNMR (400 MHz, DMSO-d 6 ) 6 -109.26 (quintet, J = 9.00 Hz, IF), - 113.52 (quartet, J = 9.52 Hz, IF), -120.62 (d, J = 9.09 Hz, 2F). LC/MS tr = 5.43 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 541 (M+H). ES-HRMS m/z 541.1128 (M+H calcd for C 2 sH 22 CIF 4 N 2 Os requires 541.1148). Example 351 yl]-3,5-difluorobenzyl}acetamide The compound was prepared in the following the produre for Example 350, substituting acety! chloride (24 mg, 0.30 mmol) for 2-acetoxy-2-methyl-propiony! chloride. (128 mg, 96%). NMR (400 MHz, DMSO-4) 6 8.48 ( br s, IH), 7.87 (d, J = 7.28 Hz, IH), 7.64 (quartet, J = 8.01 Hz, IH), 7.33, (dt, J = 2.25 Hz, IH), 7.17 (m, 3H), 6.76 (d, J = 8.25 Hz, IH), (s, 2H), 4.30 (m, 2H), 1.88(s, 3H). 19F-NMR (400 MHz, DMSO-d ) 6 -109.22 (quintet, J = 8.04 Hz, IF), -113.52 (quartet, 9.91 Hz, IF), -120.43 (d, J = 8.77 Hz, 2F) . LC/MS tr = 5.04 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic over 6 minutes at 1 ml/min with detection at 215 nm, at ES-MS m/z 555 (M+H). ES-HRMS m/z 455.0824 (M+H calcd for C 21 HIGCIF 4 N 2 0 requires 455.0780). Example 352 0 NH F N-{4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-2-oxopyridin-l(2H)- yl]-3,5-difluorobenzyl}-2-methoxyacetamide The compound was prepared in the following the produre for EXAMPLE 350, substituting 2-methoxy-acetyl chloride (45 mg, 0.415 mmol) for 2-acetoxy-2-methyl-propionyl ch!oride. (124 rag, 78%). IH-NMR (400 MHz, DMSO-dG) 6 8.56 (t, J = 6.77 Hz, IH), 7.90 (d, J = 7.85 Hz, IH), 7.67 (quartet, J = 7.67 Hz, IH), 7.36, (dt, J = 10.03, 2.36 Hz, IH), 7.20 (m, 3H), 6.79 (d, J = 8.07 Hz, IH), 5.40 (s, 2H), 4.37 (d, J = 6.28 Hz, 2}{), 3.91(s, 2H), 3.35 (s, 3 H) . 19F-NMR (400 MHz, DMSO-d ) 109.23 (quintet, J = 8.29 Hz, IF), -113.50 (quartet, J = 9.36 Hz, !F), -120.43 (d, J = 9.07 Hz, 2F). LC/MS tr = 5.13 miinutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, 50°C) ES-MS m/z 485 (M+H) . ES-HRMS m/z 485.0856 (M+H calcd for C 22 HIeCIF 4 N 2 0 4 requires 485.0886). Example 353 O NH F N-{4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-2-oxopyridin-l(2H)- yl]-3,5-difluorobenzyl}-2-furamide The compound was prepared in the following the produre for EXAMPLE 350, substituting furoyl chloride (62 mg, 0.48 mmol) for 2-acetoxy-2-methyl-propionyl chloride. Yield: 142 mg, 85%. (quintet, J = 7.65 Hz, IF), -113.50 (quartet, J = 9.84 Hz, IF), -120.29 (d, J = 9.41 Hz, 2F). LC/MS tr = 5.32 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at I ml/min with detection at 215 nm, at 50°C) ES-MS m/z 507 (M+H). ES-HRMS m/z 507.0716 (M+H calcd for C 24 HI CIF 4 N 2 0 4 requires 507.0729). Example 354 H F O N- {4- [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -2-oxopyridin-i (2H) - yl ] - 3,5 - di f i uorobenzyl } - IHimidazole - 4 - carboxami de Step i: Preparation of the title compound l-[4-(aminomethyl)-2,6-difluorophenyl]-3-chloro-4-[(2,4- difluorobenzyl)oxy]pyridin-2(IH)-one hydrochloride (150 mg, 0.334 mmol) is dissolved in a solution of 4 ml tetrahydrofuran and triethylamine (35 mg, 0.35 mmol). 4-imidazolecarboxylic acid (62 mg, 0.56 mmol), l-hydroxybenzotriazole hydrate (90 mg, 0.67 mmol), l-[3-(dimethylamino)propyl]-3- ethylcarbodiimide hydrochloride (128 mg, 0.668 mmol), and triethylamine (!00. mg, 0.989 mmol) were combined in 5 ml tetrahydrofuran and stirred under nitrogen. The solution containing I- [4-(aminomethyl)-2,6-difluorophenyl]-3-chloro-4- [(2,4-difluorobenzyl)oxy]pyridin-2(iH)-one hydrochloride was added in one portion, rinsing with 2 ml tetrahydrofuran. Stirring was continued at room temper-ature overnight, then the reaction was poured into 90 ml of icewater, and the product collected by filtration and dired in vacuo (254 mg, 94%). IHNMR (400 MHz, DMSO-d 6 ) 6 12.55 (br s, IH), 8.73 (t, J = 6.57 Hz, IH) , 7.90 (d, J = 7.87 Hz, IH), 7.75 (s, IH) , 7.67 (m, 2H), 7.35, (dt, J = 10.04, 2.54 Hz, IH), 7.21 (m, 3H), 6.78 (d, J = 8.04 Hz, IH), 5.39 (s, 2H), 4.47 (m, 2H). 19F-NMR (400 MHz, DMSO-d 6 ) 6-109.26 (quintet, J = 7.87 Hz, IF), 113.52 (quartet, J = 9.30 Hz, IF), -120.59 (d, J = 9.21 Hz, 2F). LC/MS tr = 4.48 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50oC) ES-MS m/z 507 (M+H) . ES-HRMS m/z 507.0818 (M+H calcd for C 23 HI 6 CIF 4 N 4 0] requires 507.0842). Example 355 H F N-{4-[3-chloro-4-[(2,4-diflu 0 r 0 benzyl) 0 xy]-20 x 0 pyridin1( 2 H)_ yl]-3,5-difluorobenzyl}-5-oxoprolinamide Step I: Preparation of the title compound The compound was prepared following the procedure for Example 354, substituting 2-pyrrolidone-5-carboxylic acid for 4imidazolecarboxylic acid. IH-NMR (400 MHz, DMSO-d 6 ) 6 8.67 (t, (quintet, J = 7.72 Hz, IF), -113.52 (quartet, J = 8.94 Hz, IF), -120.39 (d, J = 9.11 Hz, 2F). LC/MS tr = 4.81 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 524 (M+H). ES-HRMS m/z 524.0998 (M+H calcd for C 24 HIgCIF 4 N 3 0 requires 524.0995) . Example 356 H O 0 OH N- {4- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2 °oxopyridin-I (2H) yl ] - 3,5 - di f luorobenzyl } - 3 - hydroxy3 - met hylbut anamide Step i: Preparation of the title compound The compound was prepared following the procedure for , substituting 2-hydroxyl-2-methyl butyric acid for 4imidazolecarboxylic acid. IH-NMR (400 MHz, DMSO-d 4 ) 6 8.43 (qr, 6.84, 113.53 (quartet, J = 9.23 Hz, IF), -120.49 (d, J = 9.39 Hz, 2F). LC/MS tr = 5.08 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 513 (M+H). ES-HRMS m/z 513.1177 (M+H calcd for C 24 H 22 CIF 4 N O 4 requires 513.1199). Example 357 O I O !V- {4- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin-1 (2H) yl ] - 3,5 -di fluorobenzyl } - 1 - hydroxycyclopropanecarboxamide Step i: Preparation of the title compound The compound was prepared following the procedure for , substituting l-hydroxy-l-cyclopropanecarboxylic acid for 4imidazolecarboxylic acid. IH-NMR (400 MHz, DMSO-d ) 6 8.70 J = 6.26 Hz, IH), 7.89 (d, J = 6.31, IH), 7.65 (qr, J = 6.83, IH) , 7.34 (t, J = 10.58 Hz, IH) , 7.19 (m, 3H) , 6.77 (d, J = 7.70 Hz, IH), 5.38 (s, 2H), 4.35 (d, J = 5.66, 2H), 1.14 (s, IH), 1.02 (m, 2H), 0.84 (m, 2H). 19F-NMR (400 MHz, DMSO-d ) -109.25 (quintet, J = 8.05 Hz, IF , -113.53 (quartet, J = 8.27 Hz, IF), -120.59 (d, J = 8.99 Hz, 2F). LC/MS tr = 5.01 minutes (0-95% acetonitrile/water 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 497 (M+H). ES-HRMS m/z 497.0873 (M+H calcd for C 23 HIsCIF 4 N 2 0 4 requires 497.0886). Example 358 N- {4- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -2-oxopyridin-i (2H) yl ] - 3,5 - di f luorobenzyl ) - 2 - hydroxy2 -methylpropanamide Step i: Preparation of the title compound The compound was prepared following the procedure for , substituting 2-hydroxyisobutyric acid for 4- imidazolecarboxylic acid. IH-NMR (400 MHz, DMSO-d 6 ) 6 8.48 J = 6.41 Hz, IH), 7.89 (d, J = 7.78, IH), 7.65 (qr, J = 9.10, IH), 7.33 (dt, J = 10.12, 2.41 Hz, IH), 7.17 (m, 3H), 6.77 J = 7.69 Hz, IH), 5.38 (s, 2H), 4.31 (d, J = 6.50, 2H), 1.41 (s, IH), 1.33 (s, 6H) . 19F-NMR (400 MHz, DMSO-d ) 6-109.25 (quintet, J = 7.49 Hz, IF), -113.53 (quartet, J = 9.64 Hz, IF), -120.59 (d, J = 8.68 Hz, 2F) . LC/MS tr = 5.05 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 499 (M+H) . ES-HRMS m/z 499.1020 (M+H calcd for C 23 H 20 CIF 4 N 2 0 4 requires 499.1042). Example 359 3,5-difluorobenzonitrile Step I: Preparation of 3-bromo-4- [ (2,4difluorobenzyl) oxy] pyridin-2 (IH) -one NH O The compound was prepared in the following the produre for 3chloro-4- [ (2,4-difluorobenzyl)oxy]pyridin-2(iH)-one (, Step 3), substituting N-bromosuccinimide for N-chlorosuccinimide. IH-NMR (400 MHz, DMSO-dG) 6 11.85 (br s, IH), 7.61 (m, IH), 7.46 (d, J = 7.36 Hz, IH) , 7.30, (m, IH), 7.14 (m, IH), 6.40 (d, J = 7.71 Hz, IH), 5.26 (s, 2H). 19F-NMR (400 MHz, DMSOd 6) 6-109.69 (quintet, J = 7.93 Hz, IF), -113.63 (quartet, J = 9.55 Hz, IF). LC/MS tr = 4.48 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 316 (M+H) . Step 2: Preparation of the title compound The compound was prepared following the procedure for 4-[3chloro-4-[(2,4-difluorobenzyl)oxy]-2-oxopyridin-l(2H)-yl]-3,5difluorobenzonitrile (, Step 4), substituting 3-bromo-4-[(2,4difluorobenzy )oxyipyrid 2°(!H')-one ( from steep i) (I.92 g 6.06 mmol) for 3-chloro-4-[(2,4-difluorobenzyl)oxy]pyridin2(IH)-one (, from Step 3). IH-NMR (400 M64z, DMSO-d ) 6 8.13 ( d, J = 7.24 Hz, 2H), 7.95 (d, J = 7.76 Hz, IH), 7.66 (quartet, J = 8.71 Hz, IH), 7.34, (dr, J = 9.94, 2.53 Hz, IH), 7.17 (dt, J = 8.64, 2.33 Hz, IH) , 6.82 (d, J = 7.77 Hz, IH) , 5.39 (s, 2H) . 19F-NMR (400 MHz, DMSO-d ) 6 -109.28 (quintet, J = 7.98 Hz, IF), -113.45 (quartet, J = 9.29 Hz, IF), -116.30 (d, J = 7.44 Hz, 2F) . LC/MS tr = 5.48 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50°C) ES-MS m/z 453 (M+H) . ES-HRMS m/z 452. 9836 (M+H calcd for C 19 HI 0 BrF 4 N 2 0 2 requires 452.9856) . Example 360 3-Bromo-l-(3-fluorobenzyl)-6-methyl-4-(2-phenylethyl)pyridin2 (IH) - one Step i: Preparation of l-(3-fluorobenzyl)-4-hydroxy-6methylpyridin-2(iH)-one A mixture of 4-hydroxy-6-methyl-2-pyrone (2.5 g, 0.02 mol) and 3-fluorobenzylamine (2.5 g, 0.02 mol) in n-butanol (15 .0 mL) was heated to reflux for 16 h under argon atmosphere. Butanol wad distilled in vacuo, the residue was triturated with EtOAc, cooled and filterd the precipitate. It was washed with cold EtOAc, and dried to give 0.86 g of the title compound as a pale yellow powder: IHNMR (CD3OD/400 MHz) 6 7.31 (m, IH), 7.0 - 6.85 (m, 2H), 6.83 (d, IH, J = 9.6 Hz), 5.96 (d, IH, j = 2.0 Hz), 5.80 (d, IH, J = 2.0 Hz), 5.30 (s, 2H) , and 2,24 (s, 3H) ; ESMS m/z = 234 (MH+) . Step 2: Preparation of 3-bromo-l-(3-fluorobenzyl)-4-hydroxy6 -methylpyridin2 (IH) -one O F A mixture of l-(3-fluorobenzy!)-4-hydroxy-6-methylpyridin2(iH)-one ( 0.8 g, 0.0034 mol), NBS (0.64 g, 0.0036 mol) in dichloromethane (15.0 mL) was stirred at room temperature, under argon atmosphere. After 1.5 h, the reaction mixture was diluted with dichloromethane (15.0 mL), cooled and filterd the solids. The residue was washed with dichloromethane and dried in vacuo to give 0.93 g of the title compound as a white powder: IHNMR (CD3OD/400 MHz)6 7.33 (m, IH), 7.2 - 6.8 (m, 3H), 6.07 (s, IH) , 5.34 (s, 2H), 2.26 (s, 3H); ESHRMS m/z 312.0016 (M+H CI3HI2NO2BrF requires 312.0035). Step 3: Preparation of 3-bromo-l-(3-fluorobenzyl)-6-methyl-2oxo-l,2-dihydropyridin-4-yl trifluoromethanesulfonate To a suspension of 3-bromo-l-(3-fluorobenzyl)-4-hydroxy-6methylpyridin-2(iH)-one (0.86 g, 0.0028 mol) in dichloromethane (15.0 mL) cooled to - °C, triethyl amine (0.5 mL, 0.004 mol) and trflic anhydride (0.7 mL, 0.0042 mol) were added and stirred for 1 h. The resulting orange solution was poured into ice cold water (25 niL) and extracted with dichloromethane ( 2 x 25 mL) The combined organic extracts were washed with water, dried (Na2S04) and concentrated under reduced pressure. The resulting residue was purified by silica gel flash chromatography using I:i EtOAc/hexane v/v to afford 1.0 g (85%) the title compound as a light brown solid: IHNMR (CDC13/400 MHz) 8 7.32 (m, iH), 7.0 - 6.85 (m, 3H), 6.18 (s, IH), 5.32 (s, 2H) , and 2.34 (s, 3H) ; ESHRMS m/z 443.9492 (M+H CI4HIINO4BrF4S requires 443.9528). Step 4 : Preparation of 3-bromo-l-(3-fluorobenzyl)-6-methyl-4- (phenylethynyl) pyridin-2 (IH) -one A solution of 3-bromo-l-(3-fluorobenzyl)-6-methyl-2-oxo-l,2dihydropyridin-4-yl trifluoromethanesulfonate (i.0 g, 0.0022 mol) and phenylacetylene (0.3 mL, 0.0029 mol) in DMF (5.0 mL) was degassed using house vacuum, and purged with argon (3 cycles). Then added diisopropylethylamine, (0.5 mL) followed by the addition of PdCI2(PPh3)2 (0.36 g). The reaction mixture was heated at 65 °C for 1.5 h under argon atmosphere. The solvents were distilled in vacuo, and the residue was purified by silica gel flash chromatography using EtOAc/hexane (2:3 v/v) to afford 0.65 g (70%) of the title compound as a brown colored amorphous solid: IHNMR (CD3OD/400 MHz). 67.59 (m, 2H) , 7.45 - 7.3 (m, 4H) , 7.05 - 6.85 (m, 3H) , 6.44 (s, IH) , 5.41 (s, 2H), and 2.31 (s, 3H); 19F-NMR (CD3OD/400 MHz) 6 116.33 (m) ; ESHRMS m/z 396.0373 (M+H C21HI6NOBrF 396.0399). Step 5: Preparation of 3-bromo-l-(3-fluorobenzyl)-6-methyl-4- (2-phenylethyl)pyridin-2(iH)-one To a solution of 3-bromo-l-(3-fluorobenzyl)-6-methyl-4- (phenylethynyl)pyridin-2(IH)-one (0.55 g, 0.0014 mol) in EtOAc (I0.0 mL) and EtOH (I0.0 mL) was added PtO2 (0.05g) and stirred in an atmosphere of hydrogen gas at 15 psi for 30 min. The catalyst was removed by filtration, the filtrate was concentrated and the residue was purified by silica gel flash chromatography using 25% EtOAc in hexane as the eluent. The appropriate fractions were combined (visualized under UV) and concentrated to dryness. IHN R (CD3OD/ 00 MHz)6 7.35 (m, IH), 7.31 - 7.16 (m, 5H), 6.99(m, IH), 6.91 (m, IH) , 6.81 (m, IH), 6.20 (s, IH), 5.41 (s, 2H), 2.94 (m, 4H), and 2.24 (s, 3H) ; 19F-NMR (CD3OD/400 MHz) 6 -115.01 (m) ; ESHRMS m/z Example 361 F 3-bromo-l- (3-fluorobenzyl) -4- (l-phenylethoxy) pyridin-2 (IH) - one A mixture of 3-bromo-l-(3-fluorobenzyl)-4-hydroxypyridin2(iH)-one (0.2 g, 0.72mmol), potassium carbonate (0.I g, 0.72 mmol) and (l-bromoethyl)benzene (0.19 g, 1 mmol) in DMF (3.0 mL) was stirred at room temperature for 16 h. DMF was distilled in vacuo, and the residue was purified by flash chromatography (EtOAc in hexane (1:3 v/v) to give pale yellow syrup. This material was further purified by reverse-phase HPLC using i0 - 90% acetonitrile/water gradient (30 min), at flow rate of i00 mL/min. The appropriate fractions were combined, concentrated to a small volume (20 mL), added EtOAc (25 mL) and washed successively with satd. sod. bicarbonate, water, and dried (Na 2 SO 4 ). EtOAc was removed under reduced pressure and residue was dried in vacuo to afford the title compound (0.15 g, 52%) as an amorphous substance: IH NMR (CD 3 OD/ 400 M}{z) 6 7.56 (d, IH, J = 7.6 Hz), 7.4 - 7.2 (m, 5H), 7.0 (m, 3H), 6.28 (d, IH, J = 7.6 Hz), 5.65 (m, IH), 5.19 (d d, 2H, J = 14.8 Hz), and 1.64 (d, 3H, J = 6.4 Hz), ES-HRMS m/z 402.0492 (M+H C 20 HIBNO 2 Br, requires 402.0499) . Example 362 fluorophenyl)ethenyl]pyridin-2(1H)-one A mixture of 3-bromo-l-(3-fluorobenzyl)-2-oxo-l,2dihydropyridin-4-yl trifluoromethanesulfonate (i.0 g, 0.0023 mol), and 4-fluorostyrene (0.33 mL,, 0.0028 mol) in degassed DMF (i0 0 ml) containing diisopropyl ethyl amine (0.37 g, 0.0029 mol) was treated with PdCl 2 (PPh ) 2 (0.32 g, 0.46 mmol) and heated at 65 °C under argon atmosphere for 16 h. DMF was distilled in vacuo, and the residue was purified by flash chromatography (EtOAc/ hexane 1:4 v/v) to afford a yellow substance which was further purified by by reverse-phase HPLC using i0 - 90% acetonitrile/water gradient (30 min), at flow rate of I00 mL/min. The appropriate fractions were combined, concentrated to a small volume (20 mL), added EtOAc (25 mL) and washed successively with satd. sod. bicarbonate, water, and dried (Na 2 SO 4 ). EtOAc was removed under reduced pressure and residue was dried in vacuo to afford the title compound (0.06 g, 6%) as yellow powder: IH NMR (CD 3 OD/ 400 MHz) 6 7.68 (m, 3H), 7.39 (m, 3H), 7.27.0 (m, 5H), 6.82 (d, IH, J = 7.2 Hz), and 5.22 (s, 2H); 19F NMR(CD 3 OD/ 400 MHz)6-i13.9(m) and-115 (m) ; ES-HRMS m/z 402.0305 (M+HC 20 HIsNOF 2 Br, requires 402.0300). Example 363 4- (Benzyloxy) -3-bromo-l- [ (6-fluoropyridin-3yl) methyl] pyridin-2 (IH) -one A mixture of 4-(benzyloxy)-3-bromopyridin-2(IH)-one (0.2 0.00076 mol), 5-bromomethyl-2-fluoropyridine (0.25 g, 0.0013 tool) and pot. Carbonate (0.15 g, 0.0011 tool) in DMF (3.0 was stirred at room temperature for 16 h under argon atmosphere. DMF was distilled in vacuo and the residue partitioned between water (15 ml) and EtOAc (25 mL). The organic phase was washed with water, dried (Na 2 SO 4 ) and concentrated under reduced pressure. IH NMR (CD 3 OD/ 400 MHz) 6 8.22 (m, IH, 2.4 Hz), 7.92(m, IH), 7.82 (d, IH, J 7.6 Hz) , 7.44 - 7.31 (m 5H) , 7.03( m, IH) 6.49 (d, IH, 7.6 Hz),5.29 (s, 2H) , and 5.20 (s, 2H) ; 19F NMR(CD 3 OD/ 400 MHz) 6 -72.30 (d, J = 6.0 Hz) and -115 (m) ; ES-HRMS m/z 389. 0295 (M+H C 18 HIsN O 2 FBr, requires 389. 0309) . Example 364 3-Bromo-4- [ (2,4-difluorobenzyl)oxy] -I- (2,6dimethylphenyl ) - 6 -methylpyridin2 (IH) -one Preparation of i- (2,6-dimethylphenyl) -4-hydroxy-6-methylpyridin-2 (IH) - one A mixture of 4-hydroxy-6-methyl-2-pyrone (2.5 g, 0.02 mol) , 2,6 dimethylaniline (2.4 g, 0.02 mol), and p-toluenesulfonic acid (0.2 g) as heated at 140 °C for 3 h under nitrogen atmosphere. The reaction mixture was cooled, triturated with acetonitrile , cooled and filtered the solids. IH NMR (CD 3 OD/ 400 MHz) 6 7.22 (m, 3H ), 6.12 (d, IH, J = 1.6 Hz), 5.83 (d, IH, J = 1.8 Hz), 2.00 (s, 6H), and 1.82 (s, 3H) ; ESMS m/z 229 (M+H) . Step 2 Preparation of 3-Bromo-l- (2,6-dimethylphenyli -4-hydroxy-6methylpyridin-2 (IH) -one A mixture of l-(2,6-dimethylphenyl)-4-hydroxy-6methylpyridin-2(iH)-one (0.4 g, 0.00175 mol), and NBS (0.35 g, 0.0019 mol) in dichloromethane (i0.0 ml) was stirred at room temperature under nitrogen atmosphere. After i 11• solids were filtered, washed with dicholoromethane to give 0.42 g (78%) of the title compd as a pale yellow powder: IH NMR (CD 3 OD/ 400 MHz) 6 7.22 (m, 3H ), 6.21 (s, IH), 1.99 (s, 6H), and 1.82 (s, 3H); ESMS m/z 308/310 (M+H). Step 3 A mixture of 3-Bromo-l-(2,6-dimethylphenyl)-4-hydroxy-6methylpyridin-2(iH)-one (0.15 g, 0.00049 mol), 2,4 difluorobenzyl bromide (0.12 g, 0.00058 mol) and potassium carbonate (0.075 g, 0.00054 mol) in DMF 3.00 mL) was stirred at room temperature uder argon atmosphere for 2h. It was then heated at 60 °C for 30 min and concentrated in vacuo. The residue was purified by flash chromatography. IH N-MR (CD 3 OD/ 400 MHz) 6 7.62 (m, IH), 7.28 (m,3H), 7.04 (m, 2H), 6.68 (s, IH), 5.35 (m, IH), 1.98 (s, 6H), and 1.92 (s, 3H) ; ES-HRMS m/z 434.0574 (M+H CnHIgNO=F 2 Br, requires 434.0562). Example 365 3-Bromo-l- (2,6-dimethylphenyl) -4 - [ (4-fluorobenzyl) oxy] -6methylpyridin-2 (IH) -one The title compound was prepared by a procedure similar to the one described for Example 364. IH NMR (CD 3 OD/ 400 MHz) 6 (s, 2H), 1.98 (m, 6H), and 1.91 (s, 3H); ES-HRMS m/z 416.0670. (M+H C 21 H 20 NO 2 FBr, requires 416.0656) . Example 366 3-BromoI- (2,6-dimethylphenyl) -6-methyl-4- [ (2,4,6trifluorobenzyl) oxy] pyridin-2 (IH) -one The title compound was prepared by a procedure similar to the one described for EXAMPLE 364. IH (CD 3 OD/ 400 MHz) 6 7.19 (m, 3H), 6.95 (m, 2H), 6.69 (s, IH), 5.29 (s, 2H), 1.95 (s, 6H), andl.90 (s, 3H) ; ES-HRMS m/z 452.0471. (M+H C 21 HIsNO 2 F 3 requires 452.0468) . Example 367 3-Bromo-4-[(2,6-difluorobenzyl)oxy]-l-(2,6-dimethylphenyl)-6methylpyridin-2(iH)-one. The title compound was prepared by a procedure similar the one described for EXAMPLE 364. iH N-MR (CD 3 OD/ 400 MHz) 6 (M+H C 21 HIgNO 2 F 2 Br, requires 434.0562) . Example 368 C{ Cl F 3-Bromo-l-(2,6-dichlorophen¥1)-4-[(4-fluorobenzyl)oxy]-6methylpyridin-2(IH)-one Step 1 Preparation of l-(2,6-dichlorophenyl)-4-hydroxy-6methylpyridin-2(IH)-one CJ This compound was prepared by a procedure similar described in step 1 for EXAMPLE 364. Yield: 28%, 6 7.6 ( 2 7.48 ( IH 6. I0 (dd, IH) , 5.78 (d, IH, J = 1.91 (s, 3H) ; ( ES-MS m/z = 270 (MH÷ ) ; Step 2 Preparation of 3-bromo-l-(2,6-dichlorophenyl)-4-hydroxy-6methylpyridin-2(iH)-one This compound was prepared by a procedure similar to described in step 2 for EXAMPLE 364. Yield: 78%, IH MHz) CD 3 0D 6 7.61 (m, 2H), 7.49 (m, IH), 6.2 (s, IH), (s, 3H) ; ES-MS, m/z = 348 (MH+) . Step 3 This compound was prepared by a procedure similar to described in step 3 for EXAMPLE 364. Yield: 44%, IH NMR 67.62(d, 2H, J = 8.0 Hz) , 7.51 (m, 3H) , 7.15 (m, 2H) , 6.64 IH) , 5.33 (s, 2H) , and 2.0 (s, 3H) ; 19F NMR (CD 3 OD) 6 (m);ES-HRMS m/z 455.9541(M+H C 19 H! 4 NO 2 CI 2 BrF, requires Example 369 3-Bromo-l-(2,6-dichlorophenyl)-4-[(2,4-difluorobenzyl)oxy]-6 methylpyridin2 (IH) - one This compound was prepared by a procedure similar to described for EXAMPLE 368. requires 473.9469) . Example 370 Cl F 3-Bromo-l- (2,6-dichlorophenyl) -4- [ (2,6-difluorobenzyl) 6 -methylpyridin2 (IH) - one This compound was prepared by a procedure similar to the described for EXAMPLE 368. Yield: 78%, IH NMR (CD 3 OD/400 67.62(d, 2H, J = 8.0 Hz),7.52 (m, 2H), 7.1 (m, 2H), 6.77 (s, and 2.04 (s, 3H) ; : NMR (CD 3 OD) 6 -117.04 (m) ; ES-HRMS 473.9468 (M+H C 19 HI 3 NO 2 CI 2 BrF 2 , requires 473.9469) . Example 371 OMeO\ Br 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-(2-methoxy-6methylphenyl)-6-methylpyridin-2(IH)-one Step 1 Preparation of 4-hydroxy-l- (2-methoxy-6-methylphenyl) -6This compound was prepared by a procedure similar to described in step 1 for EXAMPLE 368. Yield: 21%, IH NMR (CD 3 OD/400 MHz) 67.3|( 1h0,6.94 (m, 2H 6.05 (d, IH, J = 5.78 (d, IH, J = 2.4 Hz), 3.76 (s, 3H) , 2.00 (s, 3H), (s, 3H) ; ES-HRMS m/z 246.1092 (M+H C 14 HI 6 N0 3 , requires 246.1123). Step 2 Preparation of 3-bromo-4-hydroxy-l- (2-methoxy-6methylphenyl) -6-methylpyridin2 (IH) - one OMeO, x Br This compound was prepared by a procedure similar to described in step 2 for EXAMPLE 368. Yield: 58%, H NMR (CD 3 OD/400 MHz) 67.34( 1h0,6.96 m (2H), 6.15 (s, IH), 3H), 1.99 (s, 3H), and 1.83 (s, 3H); ESMS m/z 324 (M+H) Step 3 This compound was prepared by a procedure similar to described for EXAMPLE 368. Yield: 60%, IH NMR (CD 3 OD/400MHz) [CD OD/400 NH4z) -IIi.64 (m), and-116.03 (m) ; ES-HRMS m/z 450.0532 (M+H CnHIgNO 3 CI BrF 2 , requires 450.0511). Example 372 4-[3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-3,5-dichlorobenzenesulfonamide Step 1 Preparation of 3,5-dichloro-4-(4-hydroxy-6-methyl-2oxopyridin-l(2H)-yl)benzenesulfonamide 0 Cl O\ Cl A mixture of 4-hydroxyl-6-me hylpyrone ((1.2 g, 0.0095 mol) 0 and 2,6-dichlorosulphanilamide (2.4 g, 0.0099 mol) was heated at 170 °C under argon for 20 min. The resulting dark colored melt was cooled and the crude material was first purified by flash chromatography (EtOAc) to give partially purified material which contained the desired product. This was further purified by reverse-phase HPLC using I0 ~ 90% CH 3 CN/Water (30 min gradient) at a flow rate of i00 mL/min. The appropriate fractions (m/z = 349 )were combined and freeze dried to afford 0.19 g of 3,5-dichloro-4-(4-hydroxy-6-methyl2-oxopyridin-l(2H)-yl)benzenesulfonamide as pale yellow solid: =H NMR (CD]OD/400 NS{z) 68.06(s, 2H), 6.]3 (d, IH, J = 1.6 Hz), 5.78 (d, IH, J = 1.6 Hz) , and 1.94 (s, 3H)) ; ES-HRMS m/z 348.9819 (M+H CnHI!N 2 0 4 SCI requires 348.9811) . Step 2 A mixture of 3,5-dichloro-4-(4-hydroxy-6-methyl-2-oxopyridinl(2H)-yl)benzenesulfonamide (0.18 g, 0.0005 mol), N- bromosuccinimide (0.I g, 0.00056 mol)in acetici acid (2.0 mL) was stirred at room temperature under argon atmosphere for 1 h. Acetic acid was removed in vacuo, the residue was dissolved in DMF (2.0 niL), and added 2,4 difluorobenzyl bromide (0.128 g, 0.0006 mol), potassium carbonate (0.i g, 0.0007 mol). The resulting mixture was stirred at room temperature for 1 h. The solvents were distilled in vacuo, and the residue was purified by flash chromatography (EtOAc/ hexane i: 3 v/v) to give 0.14 g of partially purified product. This was further purified by reverse-phase HPLC using i0 90% CH 3 CN/Water (30 min gradient) at a flow rate of I00 mL/min. The appropriate fractions (m/z = 553 ) were combined and freeze dried to afford 0.045 g of pale yellow powder. This was partitioned between EtOAc (25 ml) and 5% sod. bicarbonate. The organic phase was washed with water, dried (Na 2 SO 4 ) and concentrated under reduced pressure. This material was dried invacuo to afford the title compound (0.033 g) as a white amorphous substance: IH NM (CDC1 3 /400 MHz) 67.99(s, 2H), 7.59 (m, IH), 6.98 (m, IH), 6.85 (m, IH), 6.23 (s, IH), 5.69 (s, 2H), 5.28 (s, 2H) , 1.97 (s, 3H), and 1,76 (br, 2H) ; ES-H!9/MS m/z 552.7214 (M+H C 19 HI 4 BrCI 2 N 2 0 4 S requires 552.9197). Example 373 3-Bromo-4- [ (2,4-difluorobenzyl) oxl/] -i- (2,6-difluorophenyl) 6-methylpyridin2 (IH) -one Step i Preparation of l-(2,6-difluorophenyl)-4-hydroxy-6methylpyridin-2(iH)-one F A mixture of 4-hydroxy-6-methyl-2-pyrone (i0.0 g, 0.079 mol) and 2,6 difluoroaniline (9.5 g, 0.073 mol) was heated at °C under argon atmosphere for 20 min. The water formed was removed using a Dean-stark apparatus. The melt was cooled, the dark solid was tritutrated with EtOAc., and filtered. material was washed thoroughly with EtOAc to afford the desired product l-(2,6-difluorophenyl)-4-hydroxy-6methylpyridin-2(iH)-one 6.5 g (35%) as a light brown solid: N-MR (CD 3 OD/400 MHz) 67.56 (m, IH), 7.19 (m, 2H), 6.09 (m, 5.77 (d, IH, J = 2.4 Hz), and 1.99 (s, 3H); ES-HRMS m/z 238.0679 (M+H C 12 HI 0 NO 2 F 2 requires 238.0674). Step 2 Preparation of 3-bromo-l-(2,6-difluorophenyl)-4-hydroxy-6methylpyridin-2 (IH) -one The title compound was prepared by a procedure described in step2 for EXAMPLE 364. Yield: 79%, IH NMR (CD OD/400 MHz) 67.58 (m, IH), 7.21 (m, 2H), 6.19 (d, iH, J = 0.8 Hz), 1.99 (s, 3H); ES-HRMS m/z 315.9811 (M+H C 12 HgNO 2 F 2 Br requires 315.9779). Step 3 This compound was prepared by a procedure described in step for EXAMPLE 364. Yield : 63%, IH NMR (CD OD) 6 7.58 (m, 2H), 7.23 (m, 2H), 7,06 (m, 2H), 6.68 (s, IH), 5.36 (s, 2H), and 2.10 (s, 3H) ; 19F NMR (CD 3 OD) 6 - ll].50(m) , -115.96 (m) , and -121.93 (m) ; ES-HRMS m/z 442.0061 (M+H C 19 HI 3 NO 2 F 4 Br requires 442.0060) . Example 374 F F I 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-5iodo-6-methylpyridin-2(iH)-one A solution of 3-Bromo-4- [(2,4-difluorobenzyl)oxy]-l- (2,6difluorophenyl)-6-methylpyridin-2(IH)-one (0.3 g, 0.00068 mol) and N-iodosuccinimide (0.22 g, 0.00098 mol) in dichloroethane , containing dichloroacetic acid (0.I mL) was heated to reflux for 6 h under argon atmosphere. After the removal of the solvents under reduced pressure, the residue was partitioned between, dichloromethane (20 mL) and 5% sod. sulphite (I0 mL) . The organic phase was washed with water, dried (Na 2 S0 4 ), and concentrated under reduced pressure. The residue was purified by flash chromatography (25% EtOAc in hexane) to afford the title compound (0.125 g, 32 %) as a pale yellow powder: IH h MR (CDC1 3/400 MHz) 67.68(m, IH), 7.46 (m, IH), 7.11 (m, 2H), 6.95 (m, IH), 6.85 (m, IH), 5.23 (s, 2H), and 2.38 (s, 3H) ; !gF NMR (CDCI 3) 6-109.]5(m), -112.95 (m), -118.50 (m); ES-HRMS m/z 567.9014 (M+H C 19 HI 2 NO 2 F 4 BrI requires 567.9027) . Example 375 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-[2-(dimethylamino)-4,6difluorophenyl]-6-methylpyridin-2(iH)-one Step 1 3,5-difluoro-N-l~,N~l~-dimethylbenzene-l,2-diamine TO a solution of 2,4,6-trifluoronitrobenzene (2.58 g, 0.0145 mol) in THF (20.0 ml) was added a solution of N,Ndimethylamine in THF (8.5 mL of 2M soln) and stirred for min at 0 °C. It was then stirred at room temperature for min and concentrated to dryness. The resulting material was dissolved in EtOH (25 mL), added Pd/C (10%, 0.6 g) and hydrogenated at 50 psi for 4 h. The catalyst was removed by filtration, and the filtrate was concentrated to dryness under reducued pressure. Te residue was partitioned between sod. bicarbonate (10%, 25 mL) and EtOAc (30 mL) . The organic phase was washed with water, dried (Na 2 SO 4 ), and concentrated to dryness to afford the title compound (1.3 g, 50%) as a dark colored solid: IH NMR (CDCI]/400 MHz) 56.52(m, 2H), 3.64 ( br, 2H), and 2.65 (s, 6H) ; ES-HRMS m/z 172.0772 (M+ CsHI 0 N 2 F 2 requires 172.0810). Step 2 F O /N l-[2-(dimethylamino)-4,6-difluorophenyl]-4-hydroxy-6methylpyridin-2(IH)-one An intimate mixture of 4-hydroxy-6-methyl-2-pyrone (1.3 g, 0.0103 mol), and 3,5dif!uoro-N,N-dimethylbenzene-l,2diamine (1.4 g, 0.008 mol) was heated at 160 °C under argon for 15 min. The dark colored reaction mixture was cooled, triturated with EtOAc (15 ml), and filtered. The solids were washed with warm EtOAc, followed by hexane and dried to give the title compound as a light blue solid (0.4 g, 14 %). Analalytically pure sample was prepared by reverse-phase HPLC purification using I0 -90% CH CN/Water (30 min gradient) at a flow rate of i00 mL/min. The appropriate fractions were combined and freeze-dried to give the title compound: IH N-MR (CD 3 OD/400 MHz) 66.61(m, 2H), 6.08 (d, IH, J = 2.0 Hz), 6.78 (d, IH, J = 2.0 Hz), 2.69 (s, 6H), and 1.94 (s, 3H) ; ES-HRMS m/z 281.1084 (M+H C 14 HIsN 2 0 2 F 2 requires 281.1096). Step 2 Preparation of 3-bromo-l- [2-(dimethylamino)-4,6-difluorophenyl]-4-hydrox3,- 6-methylpyridin-2(1H)-one The title compound was prepared by a procedure described in step2 for EXAMPLE 364. Yield:71%, H NMR (CD OD/400 MHz) 66.62(m, 2H), 6.17 (s, IH), 2.67 (s, 6H), and 1.94 (s, 3H) ; ESHR/MS m/z 359.0188 (M+H C 14 HI 4 N O 2 F 2 Br requires 359.0201). Step 3 This compound was prepared by a procedure described in step 3 for EXAMPLE 364. Yield : 34%, IH NMR (CDC! 3 /400 MHz) 6762(m, IH), 6.98 (m, IH) , 6.85 (m, IH), 6.46 (m, 2H), 6.11(s, IH), 5.24 (s, 2H), 2.66 (s, 6H), and 1.98 (s, 3H) ; 19F NMR (CDCI /400 MHz) 6-108.06 (m) , -109.60 (m) , - 115.02 (m) , and -116.01 (m) ; ES-HRMS m/z 485.0451 (M+H C 21 HIsN 2 0 F 4 Br requires 485.0482). The title compound was prepared by stirring a suspension of thet product of step 3, above, (0.14 g) with 4N HCI in dioxane (0.7 mL) at room temperature for 30 min. The mixture was concentrated to dryness. IH NMR (CD 3 OD/400 MHz) 67.62(m, IH), 7.02 (m, 2H), 6.65 (m, 3H), 5.34 (s, 2H), 2.66 (s, 6H), and 2.05 (s, 3H) ; ESMS m/z = 485. Example 376 HO 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-{2,4-difluoro-6-[(2hydroxyethyl) (methyl)amino]phenyl}-6-methylpyridin-2(iH)-one The title compound was prepared by a similar procedure described for EXAMPLE 375, replacing N,N-dimethyl group by NMethyl-aminoethanol. IH NMR (CDCI /400 MHz) 6759(m, IH), 6.98 3.0 (m, IH), 2.66 (s, 6H), and 2.09 (s, 3H); ES-HRMS m/z 515.0512 (M+H C 22 H 20 N 2 0 3 F 4 Br requires 515. 0588) . Example 377 F 2- ({ [3-Bromo-l- (2,6-difluorophenyl) -6-methyl-2-oxo-l,2dihydropyridin4 -yl ] oxy } methyl ) - 5 - f luorobenzoni tri le Step 1 2-(Bromomethyl)-5-fluorobenzonitrile A mixture of 5-fluoro-2-methylbenzonitrile ( 2.0 g, 0.015 mol), NBS (3.2 g, 0.018 mol) and benzoylperoxide (0.25 g) in carbontetrachloride (25.0 ml) was heated to reflux for 6 h, under argon atmosphere. The reaction mixture was cooled and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by flash chromatography (5% EtOAc in hexane ) to afford 2-(Bromomethyl)-5fluorobenzonitrile (1.9 g, 60%) as a colorless liquid: IH NMR (CDCI /400 MHz) 67.59(m) 7.58 (m, IH), 7.38 (m, IH), and 7.25 (m, IH). Step 2 A mixture of 3-bromo-l- (2,6-difluorophenyl)-4-hydroxy-6methylpyridin-2 (IH) -one 1.0 g, 0.0032 mol), potassium carbonate (0.65 g, 0.0047 mol) and 2-(Bromomethyl) 5-fluorobenzonitrile (0.95 g, 0.0045 mol) in dimethylacetamide (15.0 ml) was stirred at room temperature under argon atmosphere. After lh, dimethylacetamide was distilled in vacuo and the residue was partitioned between dichloromethane (50 ml) and 55 citric acid (15 mL). The organic phase was washed with water, dried (Na 2 SO 4 ), and concentrated to dryness. The resulting material was triturated with EtOAc, filtered, washed with EtOAc and dried to afford the title compound (0.86 g, 60%) as a white powder: IH NMR (DMSO-d 6 /400 MHz) 67.95(m, IH) , 7.81 (m, IH), 7.68 (m, 2H), 7.37 (m, 2H), 6.79(s, IH), 5.45 (s, 2H), and 2.03 (s, 3H) ; 19FN-MR (DMSO-d 6 ) 6 -111.31 (m), - 120.34 (m);ES-HRMS m/z 449.0094 (M+H C 20 HI 3 N 2 0 2 F Br requires 449.0107). Example 378 F 0 r NH 2 . CF 3 COOH 4- { [2- (Aminomethyl) -4-fluorobenzyl] oxy} -3-bromo-l- (2,6difluorophenyl)-6-methylpyridin-2(iH)-one trifluoroacetate To a cold suspension of 2-({ [3-Bromo-l-(2,6-difluorophenyl)- 6-methyl-2-oxo-l,2-dihydropyridin-4-yl]oxy}methyl)-5fluorobenzonitrile (0.3 g, 0.00066 mol) in THF (3.0 mL), was added BH 3 .THF (i.0 mL). After stirring at room temperature for min, the reaction mixture was heated to reflux for 30 min under argon atmosphere. The resulting clear solution cooled, added MeOH (2.0 mL), concentrated under reduced pressure, and the residue was purified by reverse-phase HPLC purification using i0 -90% CH 3 CN/Water (30 min gradient) at a flow rate of I00 mL/min. The appropriate fractions (m/z= 453 M+H) were combined and freeze-dried to give the title compound (0.16 g, 43%) as its trif!uoroacetate salt: IH NMR (DMSO-d /400 MHz) 68.]9 (br, 3H), 7.65 (m, 2H), 7.37 (m, 4H), 6.78 (s, IH), 5.42 (s, 2H), 4.21 (br, 2H), and 2.04 (s, 3H) ; ZgF NMR (DMSO-d 6 /400 M!4z) 6 -112.96 (m) , and -120.41 (m); ES-HRMS m/z 453.0387 (M÷H C 20 HITN=O F Br requires 453.0420). Example 379 NH 2 N-[2-({[3-bromo-l-(2,6-difluorophenyl)-6-methyl-2-oxo-l,2dihydropyridin-4-yl]oxy}methyl)-5-fluorobenzyl]urea To a suspension of 4-{[2-(aminomethyl)-4-fluorobenzyl]oxy}-3bromo-l-(2,6-difluorophenyl)-6-methylpyridin-2(iH)-one trifluoroacetate (0.13g, 0.00023 mol) in THF (3.0 mL), was added triethyl amine (0.07 mL, 0.0005 mol) followed by the addition of trimethylsilylisocyanate (0.066 mL). The reaction mixture was stirred at room temperature for 1 h, and the desired product was isolated by reverse-phase HPLC purification using i0 -90% CH 3 CN/Water (30 min gradient) at a flow rate of i00 mL/min. The appropriate fractions (m/z= 496 M+H) were €ombine an f r e z -d i_ed and th residue was partitioned between so b ca orI -(ZO n i), an -cti b Q omethane(2 mL). The organic phase was washed with water, dried (Na 2 S0 4 ) and concentrated to dryness under reduced pressure, to afford the title compound as a white amorphous powder (0.065 g): IH NMR (DMSO-d /400 MHz) 67.62 (m, IH), 7.52 (m, IH), 7.35 (m, 2H), 7.09 (m, 2H), 6.77 (s, IH), 6.51 (t, IH), 5.61 (s, 2H), 5.38 (s. 2H), 4.28 (d, 2H, J = 6.0 Hz), and 2.02 (s, 3H) ; 19F N'MR (DMSO-d /400 MHz) 6 -114.044 (m) , and -120.31 (m) ; ES-HRMS m/z 496.0460 (M+H CnHIsN O 3 F 3 Br requires 496.0478). Example 380 OMe Methyl 2-({ [3-bromo-l-(2,6-difluorophenyl)-6-methyl-2-oxo1,2-dihydropyridin-4-yl]oxy}methyl)-5-fluorobenzylcarbamate To solution of 4-{[2-(aminomethyl)-4-fluorobenzyl]oxy}-3bromo-l-(2,6-difluorophenyl)-6-methylpyridin-2(iH)-one trifluoroacetate (0.12g, 0.00021 mol) in dimethylacetamide (2.0 mL) at 0 °C, was added triethylamine (0.06 mL, 0.00043 mol) followed by the addition of methylchloroformate (0.05 mL). The reaction mixture was stirred at room temperature for min under argon atmosphere. Dimethylacetamide was distilled in vacuo and the residue was partitioned between dichloromethane (I0 mL) and 5% citric acid (i0 mL) . The organic phase was washed with water, dried (Na 2 SO 4 ) and concentrated to dryness. The resulting residue was purified by flash chromatography (60%EtOAc in hexane) to afford the title compound (0.09 g, 75%) as white amorphous, p Qwde : iH,. (DMSO-dJ400 MHz) 6-113.77 (m), and-120.33 (m) ; ES-HRMS m/z 511.0508 (M+H C 22 HIgN 2 0 4 F 3 Br requires 511.0475) . Example 381 HN N- [2- ({ [3-bromo-l- (2,6-difluorophenyl) -6-methyl-2-oxo-i, 2dihydropyridin-4 -yl ] oxy } methyl ) - 5 - f i uorobenzyl ] - 2 - hydroxyacetamide To a suspension of 4-{ [2-(aminomethyl)-4-fluorobenzyl]oxy}-3bromo-l-(2,6-difluorophenyl)-6-methylpyridin-2(iH)-one trifluoroacetate (0.12g, 0.00021 mol) in THF (2.0 mL) at 5 °C, was added triethyl amine (0.036 g, 0.00035 mol) followed by the addition of acetoxyacetyl chloride (0.05 mL). The mixture was stirred at room temperature for 30 vain, diluted with cold water (I0 mL), and extracted the products with dichloromethane ( 2 x i0 mL). The combined organic extracts were washed with water, dried (Na 2 S0 4) and concentrated to dryness. The residue was dissolved in ethanol (0.5 mL), added IN NaoH (0.5 mL)and stirred at room temperature for 1 h. The resulting solution was diluted with water (15 mL), and extracted with dichloromethane (2 x I0 mL). The combined dichloromethane extracts were washed with water, dried (Na 2 SO 4 ) and concentrated to dryness. The residue was purified by flash chromatography (1% MeOH in EtOAc) to afford= the LiLle compound (0.032 g, 30 %) as a white amorphous powder: !H NMR (CDC1 3 /400 Hz) 67.45 (m, 2H), 7.18 (m, IH), 7.05 (m, 3H), 6.23 (s, IH), 5.24 (s, 2H), 4.56 (d, 2H, J = 6.4 Hz), 4.08 (d, 2H, J = 5.2 Hz), 2.79 (t, IH), and 2.08 (s, 3H;) I F NMR (CDC1 3 /400 MHz) 6-]I].88 (m), and-118.62 (m); ES-HRMS m/z 511.0482 (M+H C 2 H gN 2 0 4 F 3 Br requires 511.0475) . Example 382 o--/ F F Ethyl 2-({[3-chloro-l-(2,6-difluorophenyl)-6-methyl-2-oxo1,2-dihydropyridin-4-yl]oxy}methyl)-5-fluorobenzylcarbamate To solution of 4-{[2-(aminomethyl)-4-fluorobenzyl]oxy}-3- chloro-l-(2,6-difluorophenyl)-6-methylpyridin-2(iH)-one trifluoroacetate (0.3g, 0.00057 mol) in dimethylacetamide (3.0 mL) was added N-methymorpholine (0.064 g, 0.00064 mol), followed by addition of ethylchloroformate (0.06 mL) and stirred at - i0 °C, for 30 min. The solvents were distilled in vacuo and the residue was purified by reverse-phase HPLC purification using i0 -90% CH 3 CN/Water (30 min gradient) at a flow rate of I00 mL/min. The appropriate fractions (m/z= 481 M+H) were combined and freeze-dried, and the residue was partitioned between 5% sod. bicarbonate (20 mL) and dichloromethane (20 mL). The organic phase was washed with water, dried (Na 2 SO 4 ) and concentrated todryness under reduced pressure, to afford the title compound as a white amorphous powder (0.15 g, 55%): IH NMR (CD OD/400MHz) 67.61 (m, IH), 7.52 7.2 Hz ); ES-HRMS m/z 481.1118 (M+H C 23 H 21 N 2 0 4 F 3 CI requires 481.1136). Example 383 Isobutyl 2-({ [3-chloro-l- (2,6-difluorophenyl)-6-methyl2 -oxoI, 2 -dihydropyridin4 -yl ] oxy} methy! ) - 5fluorobenzylcarbamate The title compound was prepared by a procedure similar to the one described for EXAMPLE 382. Yield 57 %; IH NMR (CD 3 OD/400 MHz) 67.6] (m, IH), 7.51 (m, IH), 7.24 (~t, 2H, J = 8.0 Hz), 7.18 (m, IH), 7.06 (m, IH), 6.74 (s, IH), 5.40 (s, 2H), 4.21 (s, 2H), 3.79 (d. 2H, J = 6.8 Hz), 2.12 (s, 3H), 1.85 (m, IH), and 0.91 (d, 6H, J = 6.4 Hz) ; ES-HRMS m/z 509.1422 (M+H C 2 sH 2 sN 2 0 4 F 3 CI requires 509.1449) Example 384 Cyc!opropylmethyl 2-({ [3-chloro-l-(2,6-difluorophenyl)-6methyl-2-oxo-l,2-dihydropyridin-4-yl]oxy}methyl)-5fluorobenzylcarbamate The title compound was prepared by a procedure similar to the one described for EXAMPLE 382. Yield 46%; IH NMR (CD 3 OD/400 Hz) 67.6] (m, IH), 7.55 (m, IH), 7.24 (~ t, 2H, J = 7.6 Hz), 7.18 (m, IH) , 7.05 (m, IH), 6.73 (s, IH), 5.40 (s, 2H), 4.42 (s, 2H}, 3.83 (d, 2H, J = 7.2 Hz), 2.12 (s, 3H), i.I (br, IH) 0 0.58 (-d, 2H), and 0.22 (- d, 2H) ; ES-HRMS m/z 507.1316 (M+H C 2 sH 23 N 2 0 4 F 3 CI requires 507.1293). Example 385 CF 3 COOH l-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(IH)-one trifluoroacetate Step i 1 - [ (4 - amino2 -methylpyrimidin5-yl ) methyl] -4 -hydroxy6 - methylpvridin-2 (IH) -one A mixture of 4-hydroxy-6-methyl-2-pyrone (0.9 g, 0.007 mol) and 4-amino-5-aminomethyl-2-methylpyrimidine (I.0 g, 0.007 mol) in water (i0.0 ml) was heated at i00 °C for 1 h under argon atmosphere. The reaction mixture was cooled, and filtered the yellow precipitate. It was washed successively with cold water, ethanol, and dried in vacuo to afford the title compound (i.01 g, 51%) as a pale yellow powder: IH NMR (DMSO-d 6/400 MHz) 67.62 (s, IH), 7.04 (s, IH), 5.83 (d, 1H, J = 2.0 Hz), 5.58 (d, IH, J = 2.0 Hz), 4.92 (s, 2H), 2.24 (s, 3H), and 2.22 (s, 3H) ; ES-HRMS m/z 325.0304 (M+H C 12 HI 4 N 4 0 2 Br requires 325.0295). Step 2 l-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-bromo-4- hydroxy-6-methylpyridin-2(iH)-one A mixture of l-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4hydroxy-6-methylpyridin-2(iH)-one (0.5 g, 0.002 mol), and NBS 0.4 9, 0.002. mol)in glacial, acetic acI (5 nl ) wam= at room temperature for 1 h under argon atmosphere. Acetic acid was removed in vacuo, residue was triturated with EtOAc containing i0 % EtOH, and filtered. The pale yellow precipitate was washed with EtOAc containing 10% EtOH and dried in vacuo to afford the title compound (0.47 g, 725) as a pale yellow powder: H NMR (CDHOD/400 MHz) 67.62(s, IH), 6.09 (s, IH), 5.15 (s, 2H), 2.42 (s, 3H), and 2.33 (s, 3H) ; ES-HRMS m/z 247.1i60 (M+H C 12 HIsN 4 0 2 requires 247.1190). Step 3 To suspension of l-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3bromo-4-hydroxy-6-methylpyridin-2(iH)-one (i.0 g, 0.0031 mol) and potassium carbonate (0.0 g, 0.004 mol) in dimethylacetamide (i0.0 mL) was added 2,4 difluorobenzyl bromide (0.62 niL, 0.0048 mol) and stirred at room temperature for 2 hours. Dimethylacetamide was distilled in vacuo and the residue was purified by reverse-phase HPLC using i0 90% CHHCN/Water (30 min gradient) at a flow rate of i00 mL/min. The appropriate fractions (m/z = 566 )were combined and freeze dried to afford 0.65 g (37 %) of the title compound as its trif!uoroacetate salt: IH NMR (CD 3 OD/400 MHz) 67.65(s, IH), 7.58 (m, IH) , 7.05 (m, 2H) , 6.61 (s, IH) , 5.31 (s, 2H) , 5.18 (s, 2H) , 2.51 (s. 3H), and 2.46 (s, 3H); IH NMR (CD 3 OD/400 MHz) 6-II].39 (m), and -|15.98 (m) ; ES-HRMS m/z 451.0590 (M+H C 19 HIeN 4 0 2 BrF 2 requires 451. 0576) . Example 386 difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one hydrochloride Ion exchange (25g) BioRad AG 2X8 resin (200-.400 mesh chloride form) was washed with IM HC! (150 mL), and equilibrated for 2.5 h. This resin was loaded onto a column, and added a solution of Example 385 (3.3 g, 5.8 mmol) in water/CH 3 CN (I:i). The column was eluted slowly over 1 h, fractions were collected, and freeze dried to afford the desired HCl salt (2.2 g, 72%) as a white solid: IH-NMR (CD 3 OD, 400Hz) 6 7.60 (m, 2H) , 7.21 (m, 2H), 6.62 (s, IH) , 5.31 (s, 2H), 5.18 (s, 2H) , 2.52 (s, 3H) , 2.47 (s,3H) ; ES-HRMS m/z 451.0544/453.0577 (M+H C 19 HIvN 4© 2 F 2 Br requires 451.0581/453.0563) . Example 387 X N/ N/'/) CF 3 COO H i- [(4-amino-2-methylpyrimidin-5-yl)methyl]-3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(IH)-one trifluoroacetate Step I. Preparation of l-[(4-amino-2-methylpyrimidin-5yl)methyl]-3-chloro-4-hydroxy-6-methylpyridin-2(iH)-one 2H), 2.66 (s, 3H), 2.42 (s,3H) ; ES-HRMS m/z 281.0793 (M+H C 12 HI 3 N 4 0 2 CI requires 281.0800). Step 2. Preparation of l-[(4-amino-2-methylpyrimidin-5yl)methyl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(iH)-one trif!uoroacetate The title compound was prepared by a procedure similar to the one described for Example 385 step 2. IH NMR (CD 3 OD, 400Hz) 7.59 (m, 2H) , 7.03 (m, 2H), 6.63 (s, IH), 5.31 (s, 2H), 5.17 (s, 2H), 2.48 (s, 3H) , 2.46 (s, 3H); ES-HRMS m/z 407.1097 (M+H C 19 HIvN 4 0 2 CIF 2 requires 407. 1081) . Example 388 N/2 HCI l-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one hydrochloride Ion exchange (12.5g) BioRad AG 2X8 resin (200-400 mesh chloride form) was washed with IM HCI (150 mL), and equilibrated for 2.5 h. This resin was loaded onto a column, and added a solution of EXAMPLE 387 (1.2 g, 2.4 mmol) in water/CH 3 CN (l:l). The column was eluted slowly over i h, fractions were collected,and freeze dried to afford the desired HCI salt (1.03 g, 97%) as a white solid: IH NMR (CD OD, 400Hz) 6 7.60 (m, 2H), 7.04 (m, 2H), 6.64 (s, IH), 5.31 (s, 2H), 5.17 (s, 2H), 2.50 (s, 3H), 2.47 (s, 3H) ; ES-HRMS m/z 407.1079 (M+H C 19 HIvN 4 0 2 CIF 2 requires 407.1081) . Example 389 CF 3 COOH 3 - Bromo - 4 - [ ( 2,4 - di f luorobenzyl ) oxy] - 1 - ( IHinda zol - 5 - ylmethyl)-6-methylpyridin-2(IH)-one trifluoroacetate To a mixture of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(iH)-one (0.55 g, 0.0017 mol) and 5- (bromomethyl)-l-tetrahydro-2H-pyran-2-yl-iH-indazole (0.5 g, 0.0017 mol) in THF (I0.0 mL) was added NaH (0.045 g, 0.0019 m01) and heated at °C for 16 h under argon atmosphere. THF was distilled under reduced pressure, and the residue was suspended in EtOAc, added acetic acid (0.5 mL) and the product was purified by flash chromatography (80% EtOAc in hexane). The appropriate fractions were combined and concentrated to give an amorphous substance (0.31 g). This was stirred with trifluoroacetic (0.5 mL) for 30 min, the solution was diluted with acetonitrile (5 mL) and the product was isolated by reversephase HPLC using i0 90% CH 3 CN/Water (30 min gradient) at a flow rate of i00 mL/min. The appropriate fractions (m/z = 460 ) were combined and freeze dried to afford 0.14 g (52%) of the title compound as its trifluoroacetate salt: IH NMR (CD 3 OD/400 MHz) 67.97(s, IH), 7.62 (m, IH), 7.51 (m, IH), 7.45 (s, IH), 7.25 (m, IH), 7.03 (t, 2H), 6.49 (s, IH), 5.53 (s, 2H), 5.29 (s, 2H), and 2.40 (s, 3H); 19F NMR (CD 3 OD/400 MHz) 6 111.69 (m), -116.09 (m) ; ES-HRMS m/z 460.0432 (M+H C 21 HI N 3 0 2 BrF requires 460.0467). Example 390 H2NHN O O Br CF 3 COOH N-I-- (5- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl ] methyl } - 2 -methylpyrimidin4 -yl ) glycinamide trifluoroacetate To a solution of BOC-GIy-OH (0.19 g, 0.0011 mol) in DMF (2.0 mL), was added N-methylmorpholine (0.14 mL, 0.0011 mol), followed by the addition of isobutylchloroformate (0.15 mL, 0.0011 mol) and stirred at -I0 °C for 15 min. Then added a solution of i- [(4-amino-2-methylpyrimidin-5-yl)methyl]-3bromo-4- [(2,4-difluorobenzyl)ox ]-6-methylpyridin-2(IH)-one trifluoroacetate (0/125 g, 0.00022 mol) in DMF ( 2,0 mL) containing diisopropylethylamine (0.I g, 0.006 mL) and the resulting mixture was stirred for 16 h, at room temperature. The solvents were distilled in vacuo and the residue was purified by by reverse-phase HPLC using i0 - 90% CH 3 CN/Water (30 min gradient) at a flow rate of !00 mL/min. The appropriate fractions (m/z = 608/610) were combined and freeze dried to afford 0.025 g of white powder. This was stirred with trifluoroacetic acid (0.5 mL) for 1 h and product was isolated by reverse-phase HPLC using i0 - 90% CH 3 CN/Water (30 min gradient) at a flow rate of i00 mL/min. The appropriate fractions (m/z = 508/510) were combined and freeze dried to afford the title compound (0.02 g) as a white powder: IH NMR (CD 3 OD/400 MHz) 68.]8(s, IH), 7.61 (m, IH), 7.02 (m, 2H), 6.59 (s, IH), 5.30 (s, 4H), 4.23 (s, 2H), 2.60 (s, 3H), and 2.47 (s, 3H) ; ES-HRMS m/z 508.0797 (M+H C 22 HnNsO BrF 2 requires 508.0790). : Example 391 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-i- { [2- (methylthio) pyrimidin4 -yl ] methyl } pyridin2 (IH) -one Step 1 4-(Bromomethyl)-2-(methylthio)pyrimidine To a solution of 4-methy!-2-methylthiopyrimidine (12.6 g, 0.09 mol) in acetic acid (50.0 mL) was added bromine (5.5 mL, 0.!i mol) and heated at 80 °C under argon atmosphere for 2 h. Acetic acid was distilled in vacuo, the residue was triturated with dichloromethane (I00.0 mL] and poured into satd. sod.bicarbonate solution (200.0 mL). Additional dichloromethane (i00.0 ml) was added and stirred for 15 min. The organic phase was washed with water ( 3 x I00 mL), dried (Na 2 SO 4), and concentrated under reduced pressure. The dark colored residue was purified by flash chromatography (EtOAc/hexane 1:4 v/v) to afford 4-(bromomethyl)-2- (methylthio)pyrimidine (10.9 g, 55%) as a dark colored liquid: IH NMR (CDCI /400 MHz) 68.50(d, IH, J = 4.8 Hz), 7.09 (d, IH, J = 4.8 Hz) , 4.34 (s, 2H), and 2.56 (s, 3H); ESMS m/z 219 (M+H) . Step 2 To a mixture of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(iH)-one 5.0 g, 0.015 mol) and 4- (Bromomethyl)-2-(methylthio)pyrimidine (4.0 g, 0.018 mol) in THF (50.0 mL) was added NaH (0.4 g, 0.0017) and stirred at °C under argon for 16 h. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between 5% citric acid (25 mL) and EtOAc (50 mL). A precipitate was formed, it was filtered, washed with water, EtOAc, and dried in vacuo to afford the title compound (4.2 g, 59 %) as a light brown powder, IH NMR (CD OD/400 MHz) 6g.45(d, IH, J = 5.2 Hz), 7.6 (m, IH), 7.06 (d over m, 2H, J = 5.2 Hz), 6.54 (s, IH), 5.39 (s, 2H), 5.32 (s, 2H) , 2.43 (s, 3H) , 2.33 (s, 3H) ; ES-HRMS m/z 468.0173 (M+H C 19 HIvN 3 0 2 BrSF 2 requires 468.0187). Example 392 3-Bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- { [2- (methylsulfonyl) pyrimidin-4-yl] methyl }pyridin-2 (IH) -one A suspension of 3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl- I-{ [2_ (methylthio)pyrimidin-4-yl]methyl}pyridin-2(iH)-one 0.28 g, 0.0006 mol), and magnesium monoperoxyphthalate hexahydrate 90.6 g, 0.0012 mol) in acetonitrile (8.0 ml) and water (2.0 ml) was stirred at room temperature for 16 h. The resulting clear solution was concentrated under reduced pressure, and the residue was partitioned between dichloromethane (30 mL) and water (20 mL). The organic phase was washed with water, dried (Na 2 SO 4 ) and concentrated to afford the title compound (0.27 g, 90%) as a pale yellow substance: IH NMR (CD 3 OD/400 MHz) 68.91 (d, IH, J = 5.2 Hz) , 7.63 (d over m, 2H, J = 5.2 Hz), 7.03 (m, 2H), 6.58 (s, IH), 5.54 (s, 2H), 5.33 (s, 2H), 3.28 (s, 3H), and 2.49 (s, 3H); 19F NMR (CD OD/400 MHz) 6-111.58 (m), -115.98 (m);ES-HRMS m/z 500.0113 (M+H CIgHIvN 3 0 4 BrSF 2 requires 500.0086) . Example 393 oxopyridin-l(2H)-yl]methyl}pyrimidine-2-carbonitrile trifluoroacetate A mixture of 3-Bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-l- { [2-(methylsulfonyl)pyrimidin-4-yl]methyl}pyridin-2(iH)-one (I.0 g, 0.002 mol ) and NaCN (0.15 g, 0.0031 mol) in DMF (5.0 mL) was stirred at room temperature for 2 h under argon atmosphere. DNF was distilled in vacuo, the residue was triturated with acetonitrile (i0 mL) and water (i0 mL), and filtered the red colored precipitate. It was washed with acetonitrile and dried to afford the title compound (0.26 g). The washings and the fitrate were combined and purified by reverse-phase HPLC using I0 - 90% acetonitrile/water gradient (30 min) at a flow rate of I00 mL/min to give an additional 0.5 g of the title compound: IH NMR (CD 3 OD/400 MHz) 68.83 (d, IH, J = 5.2 Hz), 7.62 (d over m, 2H, J = 5.2 Hz), 7.00 (m, 2H), 6.58 (s, IH), 5.46 (s, 2H), 5.33 (s, 2H), and 2.47 (s, 3H) ; 19F NMR (CD OD/400 MHz) 6 - I|1.64 (m) , -116.03 (m) ; ES-HRMS m/z 447.0278 (M+H CIgHI 4 N 4 0 2 BrF 2 requires 447.0263). Example 394 difluorophenyl)-6-methylpyridin-2(iH)-one trifluoroacetate To a solution of 4-{ [3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}pyrimidine-2-carbonitrile trifluoroacetate (0.3 g. 0.00066moi) in a solvent mixture of EtOAc (15.0 mL) and acetic acid (5.0 mL), was added Pd/C (i0 % , 0.18 g) and stirred in an atmosphere of hydrogen at 15 psi for 2 h. The catalyst was removed by filtration The filtrate was concentrated to dryness and the residue was residue was purified by reverse-phase HPLC using I0 - 90% acetonitrile/water gradient (30 min) at a flow rate of i00 mL/min. The appropriate fractions (m/z = 451) were combined and freeze dried to afford (0.32 g, 645) of the title compound as its trifluoroacetate salt: IH NMR (DMSO-d /400 mHz) 68.78 (d, IH, J = 5.2 Hz), 8.28 (br, 2H), 7.62 (m, IH), 7.38 (m, IH), 7.25 (d, IH, J = 5.2 Hz), 7.18 (m IH), 6.62 (s, IH), 5.32 (s, 2H), 5.29 (s, 2H), 4.24 (s, 2H), and 2.46 (s, 3H) ; 19F N-MR (DMSO-d 6 /400 MHz) 6-]09.59 (m), -113.67 (m) ; ES-HRMS m/z 451.0530 (M+H CIgHIsN 4 0 2 BrF 2 requires 451.0576) . Example 395 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-[(2-methoxypyrimidin-4yl)methyl]-6-methylpyridin-2 (iH)-one trifluoroacetate A solution of 4-{ [3-Bromo-4- [(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}pyrimidine-2-carbonitrile trifluoroacetate (0.13 g, 0.00023 mol) in MeOH (2.0 mL) was treated with IN NaOH (0.5 mL). After stirring at room temperature for 3h, it was heated at 60 °C for an additional 3 h and left overnight room temperature. The resulting solution was diluted with acetonitrile, and purified by reverse-phase HPLC using I0 - 90% acetonitrile/water gradient (30 min) at a flow rate of i00 mL/min. The appropriate fractions (m/z = 452 ) were combined and freeze dried to afford the title compound ( 0.015 g) as a white powder: IH NMR (CD 3 OD) 68.84 (d, IH, J = 5.2 Hz) 7.62 (d, IH, J = 5.2 Hz), 7.05 (m, 2H), 6.57 (s, IH), 5.49 (s, 2H), 5.32 (s, 2H), 3.96 (s, 3H), and 2.49 (s, 3H) ; ES-HRMS m/z 452.0440 (M+H C 19 HITN 3 0 3 BrF 2 requires 452.0416) . Example 396 Methyl 4-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl2-oxopyridin-l(2H)-yl]methyl}pyrimidine-2-carboxylate trifluoroacetate The title compound was obtained as a second product in the formation of 3-Bromo-4- [(2,4-difluorobenzyl)oxy]-l- [(2methoxypyrimidin4 -yl ) methyl ] - 6 -methylpyridin-2 (IH) -one trifluoroacetate. IH NMR (CD OD/400 MHz) 58.46 (d, IH, J = 5.2 Hz) , 7.62 (m, IH) , 7.00 (m 2H) , 6.93 (d, IH, J = 5.2 Hz) , 6.55 (s, IH) , 5.39 (s, 2H), 5.32 (s, 2H) , 3.85 (s, 3H) , and 2.44 (s, 3H) ; ES-HRMS m/z 480.0340 (M+H C 20 HITN 3 0 4 BrF 2 requires 480.0365). Example 397 OH CF 3 COOH 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-[(2-hydroxypyrimidin-4_ yl)methyl]-6-methylpyridin-2(IH)-one trifluoroacetate A mixture of 4-{ [3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}pyrimidine-2-carbonitrile trifluoroacetate (0.2 g, 0.00035 mol) potassium fluoride on aluminum oxide (0.25 g) in t-butanol (5.0 mL) was refluxed for 4 h under argon atmosphere. The reaction mixture was cooled, filtered the precipitate and washed with ethanol. The combined filtrate and washings were concentrated to dryness and the residue was purified by reverse-phase HPLC using I0 90% acetonitrile/water gradient (30 min) at a flow rate of i00 mL/min. The appropriate fractions (m/z = 452) were combined and freeze dried to afford the title compound ( 0.05 g) as white powder : iH NMR (DMSO-dJ400 Mz) 57.85 (d, IH J = 6.4 Hz) , 7.64 (m, IH) 7.30 (m IH), 7.15 (m IH), 6.55 (s, IH), 6.22 (d, IH, J = 6.4 Hz), 5.28 (s, 2H), 5.12 (d, 2H), and 2.29 (s, 3H) ; 19F-NMR (DMSO-d 6/400 MHz) 6 109.69 (m) , and-113.67 (m) ; ES-HRMS m/z 438.0228 (M+H C 18 HIsN 3 0 3 BrF 2 requires 438. 0259) . Example 398 O <r NH 2 CFaCOOH 4-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]methyl}pyrimidine-2-carboxamide trifluoroacetate The title compound was obtained by a procedure described for Example 397. H NMR (DMSO-ds/400 MHz) 68.82 (d, IH J = 5.2 Hz), 8.01 (br, IH), 7.79 (br IH), 7.64 (m, IH), 7.34 (m , 2H), 7.16 (m IH), 6.62 (s, IH), 5.36 (s, 2H) , 5.30 (s, 2H), and 2.38 (s, 3H) ; 19F NMR (DMSO-ds/400 MHz) 6 - 109.64 (m), and-113.66 (m) ES-HRMS m/z 465.0385 (M+H CIgHI N 4 0]BrF 2 requires 465.0368). Example 399 NHCOOMe Methyl (4-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl] methyl }pyrimidin-2-yl) methylcarbamate To a solution of 4-{ [2- (Aminomethyl)-4-fluorobenzyl]oxy}-3bromoi- (2,6-difluorophenyl) -6-methylpyridin-2 (IH) -one trifluoroacetate (0.13 g, 0.00023 mol) in dimethylacetamide (i.0 mL), was added triethylamine (0.04 mL, 0.0003 mol), followed by the addition of methylchloroformate (0.05 mL) and stirred at 0 °C for 30 min under argon atmosphere. The reaction mixture was diluted with water (i0 mL) and extracted with EtOAc (2 x 20 mL), The combined organic extracts were washed with water, dried (Na 2 SO 4 ) and concentrated to dryness. The resulting residue was purified by flash chromatography (5% MeOH in EtOAc) to afford the title compound (0.055 g, 37%) as pale yellow powder: IH NMR (DMSO-d 6 /400 MHz) 68.65 (d, IH J = 5.6 Hz), 7.63 (IH), 7.5 (m, IH), 7.28 (m IH), 7.13 (m, 2H), 6.59 (s, IH), 5.28 (s, 4H), 5.26 (d, 2H, J = 6.0 Hz), and 2.46 (s, 3H) ; 19F NMR (DMSO-d 6 /400 MHz) 6 - 109.64 (m), and-113.71 (m) ; ES-HRMS m/z 509.0621 (M+H C IH 20 N 4 0 4 BrF 2 requires 509.0630). Example 400 methylpyrazin-2-yl)methyl]pyridin-2(iH)-one Step 1 4-hydroxy-6-methyl-l-[(5-methylpyrazin-2-yl)methyl]pyridin2 (IH) -one A mixture of 4-hydroxy-6-methyl-2-pyrone (5.0 g, 0.04 mol) and 5-aminomethyl-2-methylpyrazine (5.0 g, 0.041 mol) in water (25.0 ml) was heated at i00 °C for 1 h under argon atmosphere. The reaction mixture was cooled, and filtered the yellow precipitate. It was washed with ethanol, and dried in vacuo to afford the title compound (5.8 g, 63%) as a pale yellow powder: IH NMR (DMSO-d /400 MHz) 610.43 (br, IH), 8.38(d, 2H, J = 5.2 Hz), 5.77 (d, IH, J = 2.0 Hz), 5.58 (d, IH, J = 2.0 Hz), 4.92 (s, 2H), 2.24 (s, 3H), and 2.22 (s, 3H) ; ESMS m/z 232 (M+H). Step 2 3-Bromo-4-hydroxy-6-methyl-l-[(5-methylpyrazin-2yl) methyl ] pyridin-2 (IH) -one The title compound was prepared by a procedure described in step 2 for Example 385. Yield: 64%, IH NMR (CD 3 OD/400 MHz) 68.47 (s, IH), 8.42 (s, IH), 6.07 (s, IH), 5.38 (s, 2H), 2.51 (s, 3}{), and 2.44 (s, 3H), ESMS m/z 310 and 312 (M+H). Step 3 To a mixture of 3-Bromo-4-hydroxy-6-methyl-l-[(5methylpyrazin-2-yl)methyl]pyridin-2(!H)-one (0.45 g, 0.0015 mol), and potassium carbonate (0.25 g, 0.0018 mol) in dimethylacetamide (5.0 mL) was added 2,4 difluorobenzyl bromide (0.25 mL. 0.0019 mol)and stirred at room temperature under argon for 1 h. Dimethylacetamide was distilled in vacuo and the residue was partitioned between CH 2 C1 2 (20 mL) and water (20 mL). The organic phase was washed with water, dried (Na 2 S0 4 ) and concentrated under reduced pressure. The resulting material was purified by flash chromatography (EtOAc/hexane 4:1 v/v) as the eluent. The appropriate fractions (m/z = 451/453) were combined and concentrated under reduced pressure to give a white (0.25 g, 38% )solid. IH NMR 116.09 (m) ; ES-HRMS m/z 436.0439 (M+H C 19 HIvN 3 0 2 BrF 2 requires 436.0467) . Example 401 % j/N 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-(pyrazin-2ylmethyl) pyridin-2 (IH) -one Step 1 2Chloromethylpyrazine A mixture of 2-methylpyrazine (3.5 g, 0.037 mol), NCS (6.3 g, 0.047 mol) and benzoyl peroxide (0.05 g) was heated to reflux for 16 h under argon atmosphere. It was filtered and the filtrate was concentrated to dryness. The resulting residue was purified by flash chromatography using 30 % EtOAc in hexane to afford 2-chloromethylpyrazine as a dark colored liquid (1.7 g, 36 5): IH NMR (CD 3 OD/400 MHz) 68.75 (d, IH, J = 1.2 Hz), 8.58 (m, IH), 8.56 (m, IH), and 4.75 (s, 2H) ; ESMS m/z = 129 (M+H) . Step 2 3_Br 0 m 0-4-[(2,4-diflu 0 robenzyl)oxy]-6-methylpyridin-2(!H)-one (1.8 g, 0.0055 mol) and 2chloropyrazine (0.8 g, 0.00625) were suspended in THF (25 mL), then added NaH (0.15 g, 0.0062 mol), KI (0.I g) and the mixture was heated at 65 °C under argon atmosphere for 16 h. The reaction mixture was cooled, added acetic acid (0.5 mL) and concentrated to dryness under reduced pressure. The residue was stirred with a mixture of water (50 mL) and EtoAc (25 mL) and filtered the precipitate. It was washed with water, and acetonitrile an dried in vacuo to afford 1.7 g of light brown powder. ZH NMR (CD 3 OD/400 MHz) 68.65 (d, IH), 8.49 (m, IH), 8.47 9m, IH), 7.61 (-q, IH), 7.02 (m, 2H), 6.52 (s, IH), 5.47 (s, 2H), 5.23 (s, 2H), and 2.53 (s, 3H) ; ZgF NMR (CD 3 OD/400 MHz) 6-111.72(m), and -116.07 (m) ; ES-HRMS m/z 422.0283 (M+H CzBHIsN 3 0 2 BrF 2 requires 422.0310) . Example 402 OH 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-{ [5- (hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(IH)-one Step 1 O" "OEt Ethyl 5-methylpyrazine-2-carboxylate A solution of 5-methylpyrazine-2-carboxylic acid (15.0 g, 0.109 mol) in ethanol (70.0 mL) containing (1.5 g, 0.0079 mol) was heated to reflux for 4 h under argon atmosphere. The dark colored solution was cooled, added sod.bicarbonate (i.0 g) and concentrated under reduced pressure. The residue was partitioned between water (50 mL) and EtOAc (!00 mL) . The organic layer was washed with water (2 x 25 mL), dried (Na 2 SQ), and concentrated under reduced pressure to afford ethyl 5-methylpyrazine-2-carboxylate (12.05 g, 67%) as an orange colored liquid: IH NMR (CD 3 OD/400 MHz) 69.] (d. IH, J = 1.2 Hz), 8.62 (d, iN, J = 1.2 Hz), 4.45 (q, 2H, J = 7.2 Hz), 2.63 (s, 3H), and 1,41 (t, 3H, J = 7.2 Hz) ; ESMS m/z 167 (M+H) . Step 2 o "OEt Ethyl 5-(bromomethyl)pyrazine-2-carboxylate A solution of ethyl 5-methylpyrazine-2-carboxylate (12.0 g, 0.072 mol) in glacial acetic acid (60 mL) containing bromine (4.0 mL) was heated at 80 °C under anhydrous conditions for min. After the removal of acetic acid in vacuo, the residue was partitioned between saturated, bicarbonate (I00 mL) and EtOAc (3 x 30 mL). The combined EtOAc extracts were washed with water (2 x 25 mL), dried (Na 2 SO 4 ), and concentrated under reduced pressure. The resulting liquid was purified by flash chromatography (20 %EtOAc in hexane) to afford ethyl- (5bromomethylpyrazine-2-carboxylate (7.7 g, 44%) as an orange colored liquid: IH NMR (CD 3 OD/400 MHz) 69.18 (d. IH, J = 1.2 Hz), 8.85 (d, IH, J = 1.2 Hz), 4.71 (d, 2H), 4.47 (q, 2H, J = 7.2 Hz), and 1.42 (t, 3H, J = 7.2 Hz) ; ES-HRMS m/z 244.9942 (M+H CsHI 0 N 2 0_ 0 Br requires 244.9920) . Step 3 ° oj Ethyl 5-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl ] methyl } pyrazine - 2 - carboxylate To a mixture of 3-bromo-4- [(2,4-difluorobenzyl)oxy]-6methylpyridin-2(IH)-one (6.0 g, 0.018 mol) and ethyl 5- (bromomethyl)pyrazine-2-carboxylate (4.9 g, 0.02 mol) in THF (50.0 mL) was added NaH (0.5 g) and heated at 55 °C under argon atmosphere for 3 h. The reaction mixture was cooled , added acetic acid (1.2 ml)and concentrated under reduced pressure. The residue was triturated with water and filtered the solid. It was washed with water, followed by ethanol and dried in vacuo to afford the title compound (3.0 g, 78% )as alight brown powder: IH NMR (CD 3 OD/400 MHz) 69.10 (d. IH, J = 1.2 Hz), 8.77 (d, IH, J = 1.2 Hz), 7.61 (m, IH), 7.01 (m 2H), 6.54 (s, IH), 5.54 (s, 2H), 5.30 (s, 2H), 4.43 (q, 2H, J = 6.8 Hz), 2.52 (s, 3H), and 1,39 (t, 3H, J = 6.8 Hz) ; 19F NMR (CD 3 OD/400 MHz) 5-11].64(m), and -116.04 (m) ; ES-HRMS m/z 494.0482 (M+H C 21 HIgN 3 0 4 BrF 2 requires 494.0522). Step 4 To a suspension of ethyl 5-{ [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methy!-2-oxopyridin-l(2H)- yl]methyl}pyrazine-2-carboxylate (2.0 g, 0.004 mol) in tbutanol (15,0 mL and THF (5.0 mL) was added NaBH (0.18 g, 0.0047 mol) and the mixture was stirred at room temperature for 16 h under argon atmosphere. It was cooled, added MeOH (5.0 mL) and acetic acid (i.0 mL) and concentrated to dryness The residue was triturated with water and filtered. It was washed with water, dried in vacuo and purified by flash chromatography (1% MeOH in EtOAc to afford the title compound (0.75 g, 41%) as a pale yellow powder: IH NMR (CD 3 OD/400 MHz) 6 8.58 (d. IH, J = 1.6 Hz), 8.56 (d, IH, J = 1.6 Hz), 7.6 (m, IH), 7.01(m, 2H), 6.52 (s, IH), 5.46 (s, 2H) , 5.29 (s, 2H), 4.71 (s, 2H), and 2.54 (s, 3H) ; 19F NMR (CD 3 OD/400 MHz) 6-|1|.70(m), and -116.06 (m) ; ES-HRMS m/z 452.0394 (M+H C 19 HIvN 3 0 3 BrF 2 requires 452.0416) . Example 403 //N CF 3 COOH N-- f 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-({5- [(dimethylamino) methyl]pyrazin-2-yl}methyl)-6-methylpyridin- 2(iH)-one trifluoroacetate Step 1 CI 3-Bromo-l- { [5- (chloromethyl) pyrazin-2-yl] methyl} -4- [ (2,4difluorobenzyl) oxy] - 6-methylpyridin-2 (IH) -one Cyanurylchloride (0.42g, 0.0023 mol) was added to DMF (0.52 mL) and stirred at room temperature for 15 min. Then added dichloromethane (15 mL) followed by the addition of 3-Bromo-4- [(2,4-difluorobenzyl)oxy]-l-{ [5-(hydroxymethyl)pyrazin-2- yl]methyl}-6-methy!pyridin-2(iH)-one 1.0 g, 0.0022 mol) and reaction mixture was stirred at room temperature under argon atmosphere. After 1 h, an additional 1.0 mL of DMF was added and the reaction was allowed to proceed for another hour, when a clear solution was obtained. The solution was diluted with dichloromethane (20 mL) and washed with water, dried (Na 2 S0 4 ), and concentrated to dryness under reduced pressure. The residue was triturated with EtOAc, filtered, washed with EtOAc and dried to afford 0.79 g (77%) of the title compound as a pale yellow powder: IH NMR (CD 3 OD/400MHz) 6 8.66 (s 0 2H), 7.73 (m, IH), 7.05 (m, 2H), 6.56 (s, IH), 5.52 (s, 2H), 5.33 (s, 2H), 4.74 (s, 2H), and 2.57 (s, 3H) ; ES-HRMS m/z 470.0051 (M+H CIgHIeN 3 0 2 BrCIF 2 requires 470.0077) . Step 2 A suspension of 3-Bromo-l~{ [5-(chloromethyl)pyrazin-2yl]methyl}-4-[(2,4-difluorobenzyl)oxyJ-6-methylpyridin-2(IH)- one (0.25 g, 0.00053 mol) in THF (i.0 mL) was treated winh N,-dimethyl amine (i.0 mL of 2M soln in THF) and stirred at room temperature for 16 h. The reaction mixture was concentrated and the title compound was isolated by reversephase HPLC using i0 - 90% acetonitrile/water gradient (30 min at a f!ow rate of i00 mL/min. The appropriate fractions (m/z = 479) were combined and freeze dried to afford the title compound (0.27 g, 87%) as a white powder: IH NMR (CD 3 OD/400MHz) 68.78 (d. IH, J Hz), 8.56 (d, IH, J = 1.2 Hz), 7.61 (m IH), 7.01 (m, 2H), 6.55 (s, IH), 5.49 (s, 2H), 5.30 (s, 2H), 4.52 (s, 2H), 2.94 (s, 6H) and 2.57 (s, 3H) ; 19F NMR (CD 3 OD) = 6-ZII.56 (m) and-116.02 (m) ; ES-HF MS m/z 479.0885 (M+H C 21 H 22 NdO 2 BrF.- requires 479.0889) . Example 404 F N\ N CF 3 COOH N IOH I Me 3-Bromo-4~[(2,4-difluorobenzyl)oxy]-l-[(5-{ [(2hydroxyethyl) (methyl)amino]-methyl}pyrazin-2-yl)methyl]-6methylpyridin-2(iH)-one trifluoroacetate The title compound was prepared in a similar manner as described for Example 403, substituting N-methylaminoethanol for N, N-dimethylamine. Yield = 78%, HRMS m/z 509.0964 (N+H C 22 H 24 N 4 0 3 BrF 2 requires 509.0994). Example 405 0= \ //N CF 3 COOH Q-N Me 3-Bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-l- ({5- [ (4methylpiperazin-l-yl)carbonyl]pyrazin-2-yl}methyl)pyridin- 2(iH)-one trifluoroacetate Step 1 OH 5- { [3-Bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methy!-2oxopyridin-l(2H)-yl]methy!}pyrazine-2-carboxylic acid A suspension of ethyl 5-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]methyl}pyrazine-2-carboxylate (0.18 g, 0.002 mol) and IN NaOH (0.6 mL in l:l v/v EtOH/Water) was stirred at room temperature for 1.5 h. The reaction mixture was acidified with 5% citric acid and filtered the precipitate. It was washed with water, followed by ethanol and dried in vacuo to afford the title compound (0.14 9, 77%) as a light brown powder: :H NMR (CD 3 OD/400 MHz) = 6 9.03 (s. IH), 8.60 (s, IH) , 7.61 (m.iH), 7.00 (m, 2H), 6.52 (s, IH), 5.51 (s, 2H) , 5.30 (s. 2H) , and 2.52 (s, 3H) ; 19F NMR (CD 3 OD/400 MHz) = 8-|11.75 (m) and -116.06 (m) ; ES-HRMS m/z 466.0209 (M+H C 19 HIsN 4 0 3 BrF 2 requires 466.0209). Step 2 To a solution of 5-{ [3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}pyrazine-2-carboxylic acid (0.28 g, 0.0006 mol) in DMF (3.0 mL), at -15 °C, was added isobutylchloroformate (0.082g, 0.0006 mol), followed by the addition of N-methylmorpholine (0.06 g, 0.00063 mol) and stirred under argon for 15 min. N-methylpiperazine (0.072 g 0.00072 mol) in DMF (2.0 mL) was then added to the reaction and the mixture was stirred at room temperature for 3 h. After the removal of the solvents in vacuo, the residue was purified by reverse-phase HPLC using I0 - 90% acetonitrile/water gradient (30 min) at a flow rate of I00 mL/min. The appropriate fractions (m/z = 548) were combined and freeze dried to afford the title compound ( 0.32 g, 80% as a white powder: IH NMR (CD 3 OD/400 MHz) 68.89 (d. IH, J = 1.6 Hz), 8.73 (d, IH, J = 1.6 Hz), 7.61 (m, IH), 7.01 (m,2H), 6.56 (s, IH), 5.50 (s, 2H) , 5.30 (s, 2H) , 2.9 (s, 3H) and 2.57 (s, 3H) ; 19F NMR (CD 3 OD/400 MHz) = 6 109.36 (m) and 114.91(m) ; ES-HRMS m/z 548.1090 (M+H C 4 H sNsO 3 BrF 2 requires 548.1103). Example 406 methylpiperazin-l-yl)carbonyl]pyrazin-2-y!}methyl)pyridin2(iH)-one A solution of 3-Bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-l- ( { 5- [ (4-methylpiperazinl-yl) carbonyl]pyrazin-2yl}methyl)pyridin-2 (iH)-one trifluoroacetate (0.17 g, 0.00026 mol) in 0.1N NaOH (25 mL) was stirred at room temperature for 15 min. and extracted the product in ethyl acetate (2 x mL) . The combined organic extracts were washed with water x 20 mL), dried (Na 2 SO 4 ) and concentrated to dryness. The residue was dried in vacuo to afford the title product (0.09 g, 64%) as a white powder: IH NMR (CD 3 OD/400 MHz) 68.69 (d. IH, = 1.2 Hz), 8.67 (d, IH, J = 1.2 Hz), 7.60 (m, IH), 7.00 2H), 6.54 (s, IH), 5.50 (s, 2H), 5.30 (s, 2H), 3.78 (t, 2H, = 4.8 Hz), 3.58 (t, 2H, J = 4.8 Hz), 2.526 (s, 3H), 2.53 (t, 2H, J = 4.8 Hz), 2.44 (t, 2H, J = 4.8 Hz), and 2.31 (s, 3H); 19F NMR (CD 3 OD/400 MHz) = 6-111.65 (m) and -i16.06(m); ES-HRMS m/z 548.1123 (M+H C 24 H 25 NsO BrF 2 requires 548.1103). Example 407 oxopyridin-l(2H)-yl]methyl}-N-(2-hydroxyethyl)-Nmethy!pyrazine-2-carboxamide The title compound was prepared in a similar manner as described for Example 405 , substituting N-methylpiperazine N-methylethanolamine. Yield = 60%, IH NMR (CD 3 OD/400 MHz) 6 g.69 (d. IH, J = 1.2 Hz , 8.64 (d. J = 1.2 Hz), 7.61 (m, IH), 7.00 (m, 2H), 6.54 (s, IH), 5.49 (s. 2H), 5.30 (s, 2H), 3.81 (-t, IH), 3.66 (m, 2H), 3.56 (t, IH, J = 5.2 Hz) , 3.12 (d, 3H J = 7.6 Hz) , 2.56 s, 3H) ; 19F (CD 3 OD/400 MHz) 5-109.64 (m) and -i13.66(m); ES-HRMS m/z 523.0743 (M+H C 22 H 22 N 4 0 4 BrF 2 requires 523.0797) . Example 408 oxopyridin-l(2H)-yl]methyl]-N-(2,3-dihydroxypropyl)pyrazine-2carboxamide The title compound was prepared in a similar manner as described for EXAMPLE 405, substituting N-methylpiperazine by 3-amino-l,2-propanediol. Yield = 56%; IH NMR (CD OD/400 MHz) 69.09 (d. IH, J = 1.2 Hz), 8.70 (d. IH, J = 1.2 Hz), 7.60 (m, IH), 7.00 (m, 2H), 6.54 (s, IH), 5.53 (s. 2H), 5.30 (s, 2H), 3.80 (m, IH), 3.61 (dd, IH), 5.53 (d, 2H), J = 5.2 Hz), 3.42 (dd, IH), and 2.55 (s, 3H) ; 19F NMR (CD OD/400 MHz) 6-109.65 (m), and -I13.67(m); ES-HRMS m/z 539.0703 (M+H C 22 H 22 N 4 0 4 BrF 2 requires 539.0736). Example 409 5-{ [3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]methyl}-N-(2-hydroxyethyl)pyrazine-2-carboxamide The title compound was prepared in a similar manner as described for EXAMPLE 405, substituting N-methylpiperazine by 2-aminoethanol. Yield = 46%; IH NMR (CD OD/400 Hz) 6 9.08 (d. IH, NMR (CD OD/400 Hz) 6-1!1.67 (m) and -116.07(m) ; ES-HRMS m/z 509. 0616 (M+H C IH 20 N 4 0 4 BrF 2 requires 509. 0630) . Example 410 OMe 3-Bromo-4- [ (2,4-difluorobenzyl) oxy] -i- { [5- (methoxymethyl) pyrazin-2-yl] methyl } -6-methylpyridin-2 (IH) -one To a solution of 3-Bromo-4- [(2,4-difluorobenzyl)oxy]-l-{ [5- (hydroxymet hyl ) pyrazin2 -yl] methyl } - 6 -methylpyridin2 (IH) -one (0.35 g, 0.00078 mol) in DMF at 0 °C, was added NaH (0.022 g, 0.00092 mol) and stirred for i0 min. Iodomethane (0.05 mL) was added to the reaction and the mixture was stirred at i0 for 3 h. DMF was distilled in vacuo and the residue was partitioned between 5% citric acid and EtOAc (15.0 mL) . The organic phase was washed with water, dried (Na 2 SO 4 ) and concentrated to dryness. The residue was purified by flash chromatography (EtOAc), and the appropriate fractions were combined and concentrated to a pale yellow powder. IH NMR (CD OD/400 MHz) 6 8.59 (s), 8.55 (s, IH), 7.60 (m, IH), 6.99 (m, 2H), 6.52 (s, IH), 5.47 (s, 2H), 5.30 (s, 2H), 4.57 (s, 2H), 3.44 (s, 2H), and 2.54 (s, 3H); 19F NMR (CD OD/400 6-]||.69 (m) and -i16.09(m); ES-HRMS m/z 466.0577 (M+H C 21 HIgN O 3 BrF 2 requires 466.0572). Example 411 O--- OMe 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-({5-[(2methoxyethoxy)methyl]pyrazin-2-yl]methyl)-6-methylpyridin2 (IH) -one To a solution of 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-{ [5- (hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(IH)-one (0.25 g, 0.00055 mol) in dimethyl acetamide at 0 °C, was added NaH (0.016 g, 0.00067 mol) and stirred for min. 2-Methoxyethyl bromide (0.09 g, 0.00-65 mol) was then added , and the mixture was stirred at room temperature for 6 h. Dimethylacetamide was distilled in vacuo and the product was purified by reverse-phase HPLC using i0 - 90% acetonitrile/water gradient (30 min) at a flow rate of i00 mL/min. The appropriate fractions (m/z = 510) were combined and freeze dried to afford the title compound (0.32 g, 80%) as a white powder: IH NMR (CD 3 OD/400 Hz) 68.59 (s. IH), 8.58 (s, IH), 7.60 (m , IH), 7.02 (m, 2H) , 6.52 (s, IH), 5.45 (s, 2H), 5.29 (s, 2H), 4.67 (s, 2H), 3.71 (~t, 2H, ), 3.57 (~t, 2H), 3.34 (s, 3H), and 2.54 (s, 3H) ; ES-HRMS m/z 510.0852 (M+H C 0 HIsN 4 0 4 BrF 2 requires 510.0835). Example 412 oxopyridin-l(2H)-yl]methyl}pyrazin-2-yl)methyl carbamate To a suspension of 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l-{[5- (hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(iH)-one (0.21 g, 0.00055 mol) in THF (5.0 mL) and DMF (2.0 mL), was added 4-nitrophenylchloroformate (0.i g, 0.0005 mol) and cooled to 0 °C. Triethylamine (0.052g, 0.0005 mol) was then added, stirred at room temperature for 1 h, and at 65 °C for an additional lh. It was cooled in an ice bath and added 2M ammonia in propanol (i.0 mL) and stirred at room temperature for 2 h. After the removal of the solvents under reduced pressure, the residue was partitioned between 5% sod. bicarbonate, and EtOAc (25 mL). The organic phase was washed with 5% sod. bicarbonate, (3 x 25 mL), water (3 x 25 mL), dried (Na SO 4 ) and concentrated under reduced pressure. The resulting substance was purified by isolated by reverse-phase HPLC using I0 -90% CH 3 CN/Water (30 min gradient) at a flow rate of i00 mL/min. The appropriate fractions (m/z= 495 M+H) were combined and freeze-dried, and the residue was partitioned between 5% sod. bicarbonate (20 mL) and EtOAc (25 mL). The organic phase was washed with water, dried (Na 2 SO 4 ) and concentrated to dryness under reduced pressure, to afford the title compound as a white powder (0.065 g) : (m) , and -116.09 (m) ; ES-HRMS m/z 495. 0449 (M+H C 20 HIsN O 4 BrF 2 requires 495.0474) . Example 413 i - benzyl - 3 - bromo2 -oxoi, 2 - dihydr0pyr idi n4 -yl methyl (phenyl) carbamate Step I. Preparation of l-benzyl-2-oxo-l,2-dihydropyridin-4-yl methyl(phenyl)carbamate To a chilled solution of l-benzyl-4-hydroxypyridin-2(IH)- one (0.375 g, 1.86 mmol) in anhydrous acetonitrile (i0 mL) was added triethylamine (0.206 g, 2.04 mmol) followed by N-methylN-phenylcarbamoyl chloride (0.379 g, 2.24 mmol) . The reaction mixture was stirred under nitrogen atmosphere at 0° C for minutes then at room temperature for hour. The reaction was monitored by TLC (5% methanol in dichloromethane) . The solvent was removed under reduced pressure and the residue was washed with 10% citric acid and extracted with ethyl acetate. The organic extracts were combined, washed with water and dried over anhydrous Na 2 SO 4 . The solvent was removed under reduced pressure to afford a yellow syrup. The residue was purified by flash chromatography (silica gel) using 5% MeOH in CH 2 C1 2 to give the desired product (0.382g, 61%) as a white semisolid. IH-NMR (d 6 -DMSO, 400 MHz) 67.8 (d, IH, J= 7.2 Hz), 7.39 (m, 10H), 6.19 (s, 2H), 5.03 (s, 2H), 3.29 (s, 3H) ; ESHRMS m/z 335.1396 (M+H calculated for Cz 0 HIgN 2 0 3 requires 335.1418). Step 2. ?reparation of l-benzy!-3-bromo-2-oxo-l,2dihydropyridin-4-yl methyl(phenyl)carbamate To a solution of l-benzyl-2-oxo-l,2-dihydropyridin-4-yl methyl(phenyl)carbamate (0.38 g, 1.13 mmol) in anhydrous CH 2 C1 2 (7 mL) was added N-Bromosuccinimide (hTBS, 0.24 g, 1.34 mmol) . The reaction was stirred overnight at room temperature under nitrogen atmosphere. The reaction mixture was purified by flash chromatography (silica gel) using ethyl acetate/hexane (i:i v/v). The appropriate fractions were collected according to ES MS (M+H 413) and concentrated. The dried product showed about 14% of di-bromonated product by analytical HPLC. The compounds were separated by reverse phase HPLC using a 10-90% acetonitrile in water (30 minute gradient) at a I00 mL/min flow rate to afford (after lyophilization) the salt of the desired compound. The salt was diluted in ethyl acetate and washed with NaHCO 3 . The organic extracts were dried over anhydrous Na 2 S0 4 and concentrated to afford the desired compound (0.271 g, 58%) as a beige solid. IH-NMR (d 6 -DMSO, 5.12 (s, 2H), 3.33 (s, 3H) ; ES-HRMS m/z 413.0495 (M+H calculated for Cz 0 HIBO 3 Br requires 413.0496). Example 414 CH 4-(benzyl 0 xy)-3-ethynyl-l-(3-flucrobenzyl)pyridin-2(IH)-one Step i. Preparation of 4-(benzyloxy)-l-(3-fluorobenzyl)-3iodopyridin-2(IH)-one A mixture of 4-(benzyloxy)-l-(3-fluorobenzyl)pyridin- 2(iH)-one (4.83 g, 15.6 mmol) in anhydrous acetonitrile (55 mL) and N-iodosuccinimide (NIS, 3.86 g, 17.1 mmol) was heated at 65° C under nitrogen for 4 hours. The reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (silica gel) using ethyl acetate/hexane (i:I v:v). The appropriate fractions were collected according to ES MS (M+H 436) and washed with Na 2 SO 3 to remove the color impurities. The fractions were concentrated under reduced pressure and dried in vacuo to afford the desired product (6.15 g, 90%) as a light yellow J= 8.0 Hz), 5.29 (s, 2H), 5.19 (s, 2H) ; ES-HRMS m/z 436.0210 (M+H calculated for C 19 HI 6 NO 2 FI requires 436.0196). Step 2. Preparation of 4-(benzyloxy)-!-(3-fluorobenzyl)-3- [ (trimethylsilyl) ethynyl] pyridin-2 (IH) -one TMS I c Degassed a solution of 4-(benzyloxy)-l-(3-fluorobenzyl)- 3-iodopyridin-2(iH)-one (2.01 g, 4.62 mmol) in anhydrous acetonitrile (25 mL) under argon atmosphere. Triethylamine (i.ii g, ii mmol) was added and quickly degassed. The reaction mixture was chilled in an ice bath for 15 minutes before adding bistriphenylphosphine-palladium chloride (0.34 g, 0.48 mmol) and cuprous iodide (0.2 g). The reaction was stirred at room temperature for 30 minutes before heating at 60° C under an atmosphere of argon for 2 hours. The reaction mixture was filtered through a bed of celite and the filtrate was concentrated under reduced pressure. The dark brown residue was diluted with CH 2 C] 2 (i00 mL) and washed with water. The organic extracts were combined, dried over anhydrous Na 2 SO 4, and concentrated under reduced pressure. The dark brown residue was purified by flash chromatography using 30% ethyl acetate in hexane. The appropriate fractions were combined and concentrated under reduced pressure to afford the desired product (1.34 g, 72%) as a light yellow solid. IH-NMR (CD 3 OD, 400 MHz) 64 (d, IH, J= 7.6 Hz), 7.47 (d, 2H, J= 7.6 Hz), 7.35 (m, 4H} 09 (m, 3H), 6.46 (d, IH, J= 7.6 Hz), 5.26 (s, 2H), 5.13 (s, H), 0.18 (s, 9H) ; ES-HRMS m/z 406.1638 (M+H calculated for C 24 H 2 sNO 2 FSi requires 406.1610). Step 3. Preparation of 4-(benzyloxy)-3-ethynyl-l-(3fluorobenzyl)pyridin-2(iH)-one CH To a solution of 4-(benzyloxy)-l-(3-fluorobenzyl)-3- [(trimethylsilyl)ethynyl]pyridin-2(iH)-one (1.31 g, 3.2 mmol) in anhydrous acetonitrile (25 mL) at 0° C was added tetrabutylammoniun fluoride (0.611g, 1.93 mmol) . The reaction was stirred at 0° C for 15 minutes then for 1 hour at room temperature. The reaction was concentrated under reduced pressure and the residue was diluted with ethyl acetate and washed with water. The organic extracts were combined, dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel) using ethyl acetate in hexane (i:i v/v). The appropriate fractions were combined and concentrated under reduced pressure to afford the desired product (0.779 g, 72%) as a gold solid. IH-NMR (CD 3 OD, 400 MHz) 67.73 (d, IH, J= 7.6 Hz), 7.43 (d, 2H, J= 7.2 Hz), 7.35 (m, 4H), 7.09 (m, 3H), 6.45 (d, IH, J= 7.6 Hz), 5.27 (s, 2H), 5.13 (s,2H), 3.78 (s, IH) ; ESHRMS m/z 334.1243 (M+H calculated for C 21 HIvNO 2 F requires 334.1234). Example 415 4-(benzy!amino)-3-bromo-l-(3-fluorobenzyl)pyridin-2(iH)-one Step I. Preparation of l-(3-fluorobenzyl)-4-hydroxypyridin2(iH)-one HO. -0 F In a Fischer-Porter bottle, added a solution of 4- (benzyloxy)-l- (3-fluorobenzyl)pyridin-2(iH)-one (4.5 g, 14.56 mmol) in absolute ethanol (20 mL) . Flushed the solution with nitrogen then added palladium catalyst (1.05 g, 10% Pd/C) . Sealed bottle and evacuated system. The system was purged with hydrogen gas (2 X 15 psi) to check for leaks. The reaction was charged with hydrogen (35 psi) and stirred at room temperature for 45 minutes. The system was evacuated and flushed with nitrogen. The reaction was filtered and the catalyst was carefully washed with fresh ethanol. The filtrate was concentrated under reduced pressure. IH-NMR (CD 3 OD, 400 MHz) 67.54 (d, IH, J= 7.6 Hz), 7.32 (m, IH), 7.06 (d, IH, J= 7.6 Hz), 6.99 (m, 2H), 6.05 (dd, IH, J= 2.4 Hz, 2.8 Hz) , 5.83 (d, IH, J= 2.4 Hz), 5.09 (s, 2H) ; ES-HRMS m/z 220.0774 (M+H calculated for C 12 HIINO 2 F requires 220.0787) . Step 2. Preparation of 4- (benzylamino)-l- (3fluorobenzyl ) pyridin2 (IH) -one A mixture of i- (3-fluorobenzyl)-4-hydroxypyridin-2(IH)- one (1.005 g, 4.5 mmol) in benzylamine (15 mL) was heated at reflux (185° C) under nitrogen atmosphere for 24 hours. The reaction was monitored by ES-MS (MH÷ 309). The solvent was removed by vacuum distillation to give a yellow residue. IHNMR (CD 3 OD, 400 MHz) 67.31 (m, 7H), 7.03 (m, 3H), 5.98 (d, IH, J= 7.2 Hz), 5.45 (s, IH), 5.00 (s, 2H), 4.30 (s, 2H); ES-HRMS m/z 309. 1403 (M+H calculated for C 19 HIsN 2 OF requires 309.1375}. Step 3. Preparation of 4- (benzylamino)-3-bromo-l- (3fluorobenzyl) pyridin-2 (IH) -one To a solution of 4-(benzylamino)-l-(3fluorobenzyl)pyridin-2(iH)-one (0.50 g, 1.62 mmol) In anhydrous CH 2 C1 2 (i0 mL) was added N-bromosuccinimide (NBS, 0.30 g, 1.7 mmol). The reaction was stirred at room temperature under a nitrogen atmosphere for 3 hours. The reaction mixture was purified by flash chromatography (silica gel) using ethyl acetate in hexane (I:i v/v). The appropriate fractions were combined and concentrated. IH-NMR (CD 3 OD, 400 MHz) 67.41 (d, IH, J= 7.6 Hz) , 7.31 (m, 6H), 7.04 (m, 3H) , 5.99 (d, IH, J= 7.6 Hz), 5.08 (s, 2H), 4.53 (s, 2H); ES-HRMS m/z 387.0508 (M+H calculated for C 19 HITN 2 OBrF requires 387.0504). Example 416 4-(benzyloxy)-l-(3-fluorobenzyl)-3-methylpyridin-2(1H)-one Step I. Preparation of 4-(benzyloxy)-l-(3-fluorobenzyl)-3iodopyridin-2(IH)-one F I A mixture of 4-(benzyloxy)-l-(3-fluorobenzyl)pyridin2(IH)-one (4.83 g, 15.6 mmol) and N-iodosuccinimide (NIS, 3.86 g, 17.1 mmol) in anhydrous acetonitrile (55 mL) was heated at 65° C for 4 hours under nitrogen atmosphere. The reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (ethyl acetate/hexane i:I v/v). The appropriate fractions were collected according to ES MS (M+H 436) and washed with Na 2 SO to remove the color impurities. The fractions were concentrated under reduced pressure and dried in vacuo to afford the desired product (6.15 g, 90%) as a light yellow solid. IH-NMR (CD 3 OD, 400 MHz) 67.73 (d, IH, J= 7.6 Hz), 7.36 (m, 6H), 7.08 (m, 3H), 6.39 (d, IH, J= 8.0 Hz), 5.28 (s, 2H), 5.19 (s, 2H) ; ES-HRMS m/z 436.0196 (M+H calculated for C 19 HI NO 2 FI requires 436.0210). Step 2. Preparation of 4-(benzyloxy)-l-(3-fluorobenzyl)-3methylpyridin-2(iH)-one To a degassed solution of 4-(benzyloxy)-l-(3fluorobenzyl)-3-iodopyridin-2(iH)-one (1.03 g, 2.36 mmol) in anhydrous DMF 15 mL) under argon atmosphere was added triethylamine I.Ii g, ii mmol) . The reaction mixture was chilled in an ice bath for 15 minutes before adding tetramethyl tin (2.10 g, 11.75 mmol) followed by bistriphenylphosphine-palladium chloride (0.166 g, 0.24 mmol) The reaction was stirred at room temperature for 30 minutes before heating at 95° C under an atmosphere of argon for 3 hours. The reaction mixture was filtered through a bed of celite and the filtrate was concentrated under reduced pressure. The dark brown residue was diluted with ethyl acetate (I00 mL) and washed with water. The organic extracts were combined, dried over anhydrous Na 2 SO 4 , and concentrated under reduced pressure. The dark brown residue was purified by flash chromatography (30% ethyl acetate in hexane). The appropriate fractions were combined and concentrated under reduced pressure to afford the desired product (0.1758 g, 22%) as a light yellow solid. The product was further purified by reverse phase HPLC using a 10-90% acetonitrile/water (30 minute gradient) at a I00 mL/min flow rate, to afford a cleaner product as a light yellow solid (0.0975g, 8%). IH-NMR (CD 3 OD, 400 MHz) 67.58 (d, IH, J= 7.6 Hz)), 7.35 (m, 6H), 6.98 (m, 3H), 6.46 (d, IH, J= 7.6 Hz), 5.19 (s, 2H), 5.15 (s, 2H), 2.0 (s, 3H) ; ES-HRMS m/z 324.1366 (M+H calculated for C= 0 HIgNO 2 requires 324.1394). Example 417 I- (3fluorobenzyl) -4 - [ (4 - fluorobenzyl) oxy] -3 -iodopyridin2 (IH) -one Step I: Preparation of i- (3-fluorobenzyl)-4-hydroxy-3iodopyridin-2 (IH) -one F I To a mixture of l-(3-fluorobenzyl)-4-hydroxypyridin2(IH)-one (i.i g, 5 mmol) in acetonitrile (15 mL) was added iodosuccinimide (i.i g, 5.5 mmol) along with a ca. amount of dichloroacetic acid (0.i mL) . The reaction mixture stirred room temperature for 1 hour under nitrogen. The mixture was chilled in an ice bath and filtered cold with fresh MeCI 2 . The beige solid was dried to afford the desired iodinated intermediate (l.21g, 69%). ES-LRMS m/z 346. Step 2: Preparation of l-(3-fiuorobenzyl)-4- [(4fluorobenzyl)oxy]-3-iodopyridin-2(IH)-one To a mixture of l-(3-fluorobenzyl)-4-hydroxy-3iodopyridin-2(iH)-one (0.5g, 1.44 mmol) in DMF (5 niL) was added K 2 CO 3 (0.199g, 1.44 mmol) followed by the addition of 4fluorobenzyl bromide (0.189 mL, 1.51 mmol) . The reaction mixture stirred at room temperature for 30 minutes. The mixture was diluted with ethyl acetate (50 mL) and washed with water. The organic extracts were dried over anhydrous Na 2 SO 4 and concentrated to dryness. IH-NMR (CD 3 OD, 400 MHz) 67.75 (d, IH, J= 7.6 Hz) , 7.49 (q, 2H) , 7.34 (q, IH), 7.11(m, 5H) , 6.40 (d, IH, J= 7.6 Hz), 5.26 (s, 2H), 5.19 (s, 2H) ; ES-HRMS m/z 454.0098 (M+H calculated for C 19 HIsNO 2 F 2 I requires 454.0110). Example 418 l-(3-f!uorobenzyl)-4-[(4-fluorobenzyl)oxy]-3-methylpyridin2(IH)-one To a degassed solution of l-(3-fluorobenzyl)-4-[(4fluorobenzyl)oxy]-3-iodopyridin-2(iH)-one (0.804g, 1.7 mmol) in DMF (I0 mL) and LiCI (0.25g, 5.9 mmol) was added tetramethyltin (0.49 mL, 3.54 mmol) followed by bistriphenylphosphine-palladium chloride catalyst (0.124g, 0.177 mmol). The reaction mixture was heated in an oil bath (85°-90° C) under nitrogen for 3 hours. The solvent was concentrated and the residue was diluted with ethyl acetate and washed with water. The organic extracts were dried over anhydrous Na 2 SO 4 and concentrated to dryness. The residue was purified by flash column chromatography (20% ethyl acetate in hexane). The appropriate fractions were concentrated. IH-NMR 5.15 (s, 2H) , 1.99 (s, 3H) ; ES-HRMS m/z 342.1314 (M÷H calculated for C 20 HIsNO 2 F 2 requires 342.1300). Example 4 19 F !-benzyl-3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methylpyridin2 (IH) -one To a degassed cold solution of DMF (I0 mL) and PPh (resin, 0.93 g, 2.75 mmol) was added DEAD (0.44 mL, 2.75 mmol) . The reaction mixture stirred at -10°C for 20 minutes under nitrogen. A solution of l-benzyl-3-bromo-4-hydroxy-6methy!pyridin-2(iH)-one (0.62 g, 2.1 mmol and 2,4difluorobenzylalcohol (0.283 mL, 2.5 mmol in DMF (i0 mL) was added to the resin suspension. The reaction mixture stirred at -i0° C for 30 minutes and then allowed to stir at room temperature for 1 hour. The resin was filtered and rinsed with fresh MeOH and the filtrate was concentrated. The residue was dissolved in ethyl acetate and purified by flash column chromatography (ethyl acetate/hexane I:I v/v). The appropriate fractions were concentrated. IH-NMR (CD 3 OD, 400 MHz) 6 7.62 (m, IH), 7.31 (m, 3H), 7.1 (d, 2H, J= 7.2 Hz), 7.02 (t, 2H, J= 8.6 Hz), 6.48 (s, IH), 5.42 (s, 2H), 5.28 (s, 2H), 2.34 (s, 3H) ; ES-HRMS m/z 420.0399/422.0380 (M+H calculated for C 20 HITNO 2 F 2 Br requires 420.0405/422.0387). Example 420 4-fluorobenzamide Step I. Preparation of 4-amino-l-(3-fluorobenzyl)pyridin2(IH)-one .NH 2 In a Fischer-Porter bottle, added a solution of 4- (benzylamino)-l-(3-fluorobenzyl)pyridin-2(IH)-one (2.5g, 8.11 mmol) in glacial acetic acid (20 mL). After the solution was flushed with nitrogen, catalyst was added (10%Pd/C, 2.0g). The vessel was sealed, evacuated, and purged with hydrogen gas. The system was charged with hydrogen gas (50psi) and the mixture stirred at room temperature for 4 hours. The system was evacuated and flushed with nitrogen. The reaction mixture was filtered through a bed of celite and washed with fresh ethanol. The filtrate was concentrated under reduced pressure and the residue was purified by flash column chromatography (hexane/ethyl acetate 3:4 v/v). The filtrate was concentrated. H-NMR (CDHOD, 400 MHz) 6 7.32 (q, IH), 7.02 (m, 3H), 5.93 (dd, IH, J= 2.4 Hz, 2.8 Hz), 5.58 (d, IH, J= 2.4 Hz) ; ES-HRMS m/z 219. 0966 (M+H calculated for CI 2 HI 2 N 2 OF requires 219.0928 Step 2. Preparation of 4-fluoro-N-[!-(3-f!uorobenzyl)-2-oxo1,2-dihydropyridin-4-yl]benzamide F F HO N / "TJ To a solution of 4-amino-l-(3-fluorobenzyl)pyridin-2(1H)- one (0.263 g, 1.2 mmol) in acetonitrile (7 mL) was added a DN.AP (ca.), triethy!amine (0.25 mL, 1.8 mmol) and 4fluorobenzoyl chloride (0.213 mL, 1.8 mmol). The reaction mixture stirred at 0° C for 25 minutes and then filtered. solid was washed with 10% citric acid and water to afford desired compound (0.326 g, 79%) after drying. 1H-NNR (dsDMSO, 400 MHz) 6 7.98 (m, 2H), 7.71 (d, 1H, J= 7.6 Hz), 7.35 (m, 7.08 (m, 3H), 6.98 (d, 1H, J= 2.4 Hz), 6.61 (dd, 1H, J= 2.4 Hz, 2.4 Hz) , 5.03 (s, 2H) ; ESLRNS m/z 341.1. Step3. Preparation of N-[3-bromo-l-(3-fluorobenzyl)-2-oxo1,2-dihydropyridin-4-yl]-4-fluorobenzamide To a mixture of 4-fluoro-N-[l-(3-fluorobenzyl)-2-oxo-l,2- dihydropyridin-4-yl]benzamide (0.305g, 0.89 mmol) in acetonitrile (7 mL) was added NBS (0.159g, 0.89 mmol). The reaction mixture stirred at room temperature for 1.5 hours. The filtrate was removed under reduced pressure and the residue was purified by flash column chromatography (ethyl acetate/hexane i:i v/v). The fractions were concentrated. NMR (CD OD, 400 MHz) 6 8.03 (m, 2H), 7.79 (d, IH, J= 7.6 Hz), 7.47 (d, IH, J= 8.0 Hz), 7.28 (m, 3H), 7.12 (m, 3H), 5.23 2H) ; ES-HRMS m/z 419.0202/421.0191 (M+H calculated for C 19 HI 4 N 2 0 2 F 2 Br requires 419.0201/421.0183). Example 421 F CI 0 F 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-6methylpyridin-2 (IH) -one Step i. Preparation of 3-chloro-l-(2,6-difluorophenyl)-4hydroxy-6-methylpyridin-2(1H)-one OH Cl, To a mixture of l-(2,6-difluorophenyl)-4-hydroxy-6methylpyridin-2(IH)-one (0.30 g, 1.26 mmol) in dichloromethane (5 mL) was added NCS (2.52 g, 1.90 mmol). The reaction mixture stirred at room temperature under nitrogen for 4.5 hours. The suspension was cooled in ice bath, filtered, and the solid was rinsed with fresh dichloromethane to afford the desired product (0.271 g, 79%) as a white solid. IH-NMR (CD 3 OD, 400 MHz) 8 7.58 (m, IH), 7.22 (m, 2H), 6.20 (s IH), 2.00 (s, 3H); ES-HRMS m/z 272.0287 (M+H calculated for C 12 HgNO 2 F CI requires 272.0290). Step 2. Preparation of 3-chloro-4- [(2,4-difluorobenzyl)oxy]- l- (2,6-difluorophenyl) - 6-methylpyridin-2 (IH) -one To a solution of 3-chloro-l-(2,6-difluorophenyl)-4hydroxy-6-methylpyridin-2(iH)-one (0.27 g, 1.00 mmol) in DMA (5 mL) was added K 2 C0 3 followed by the addition of 2,4dif!uorobenzyl bromide (0.128 mL, 1 mmol). The reaction mixture stirred a5 room temperature for 2 hours and then was diluted in water. The reaction mixture was extracted with ethyl acetate, the organic extracts were dried over Na 2 S0 4 and the filtrate was concentrated. The resulting residue was purified by flash column chromatography (ethyl acetate/hexane 3:4 v/v) to afford the desired product. IH-NMR (CD 3 OD, 400 MHz) 6 7.60 (m, 2H), 7.25 (m, 2H), 7.04 (m, 2H), 6.71 (s, IH), 5.36 (s, 2H) , 2.11 (s, 3H) ; ES-HRMS m/z 398.0551 (M+H calculated for C 19 HI 3 NO 2 F 4 CI requires 398.0571). Example 422 3-bromo-l-(4-fluorobenzyl)-4-[(4-fluorobenzyl)amino]-6methylpyridin-2 (IH) -one Step i: Preparation of l-(4-fluorobenzyl)-4-[(4fluorobenzyl)amino]-6-methylpyridin-2(iH)-one s A mixture of 4-hydroxy-6-methylpyrone (5.0 g, 0.04 mol) and 4-fluorobenzylamine (10.0 g. 0.08 mol) in n-butanol (25.0 n ) was heated to reflux for 24 hours under argon atmosphere. The resulting solution was concentrated to dryness under reduced pressure. The residue was triturated with ethyl acetate and filtered. It was thoroughly washed with ethyl acetate and dried to afford the title compound as a pale yellow powder (4.1 g. 30%). IH-NTMR (CD 3 OD, 400 MHz) 6 7.33 2H), 7.04 (m, 5H), 5.85 (d, !H, J= 2.0 Hz), 5.44 (d, 2H, J= 2.4 Hz) , 5.20 (s, IH) , 4.29 (s, 2H), 2.17 (s, 3H) ; ES-HRMS 341.1488 (M+H calculated for C 20 H:gN 2 OF 2 requires 341.1460). Step 2: Preparation of 3-bromo-l-(4-fluorobenzyl)-4-[(4fluorobenzyl)amino]-6-methylpyridin-2(IH)-one To a solution of l-(4-fluorobenzy!)-4-[(4fluorobenzyl)amino]-6-methy!pyridin-2(iH)-one (0.2857 g, 0.84 mmol) in MeCI 2 was added NBS (0.156 g, 0.88 mmol). The reaction stirred at room temperature under nitrogen for minutes. The reaction mixture was diluted with MeCI 2 and washed with NaHCO 3 . The organic extracts were washed with water, dried over Na 2 S0 4 , and concentrated to afford the desired product (0.3242 g, 92%) as a yellow solid. IH-NMR (CD 3 OD, 400 MHz) 6 7.32 (q, 2H), 7.04 (m, 6H), 5.91 (s, IH), 5.28 (s, 2H), 4.50 (s, 2H), 2.17 (s, 3H) ; ES-HRMS m/z 419.0549/421.0537 (M+H calculated for C 20 HIsN 2 OBrF 2 requires 419.0565/421.0547). Example 423 F s/ 0 3-bromoi- (cyclopropylmethyl) -4- [ (2,4-difluorobenzyl) oxy] methylpyridin-2 (IH) -one To a mixture of 3-bromo-l-(cyclopropylmethyl)-4-hydroxy6-methylpyridin-2(iH)-one (0.276 g, 1.07 mmo!) and K 2 C0 3 (0.148 g, 1.07 mmol) in DMA (4 mL) was added 2, 4-dif!uorobenzy! bromide (0.14 ml, 1.07 mmol). The mixture stirred at room temperature for 1.5 hours. The reaction mixture was diluted in water and extracted with ethyl acetate. The organic extracts were dried over Na 2 SQ and concentrated. The residue was purified by flash column chromatography (ethyl acetate!hexane i:I v/v) . The appropriate fractions were combined, and concentrated. IH-NMR (CD 3 OD, 400 MHz) 6 7.60 (q, IH), 7.04 (m, 2H) , 6.42 (s, IH), 5.26 (s, 2H), 4.06 (s, !H), 4.04 (s, IH), 2.50 (s, 3H), 0.53 (m, 2H), 0.43 (m, 2H); ESHRMS m/z 384.0392 (M+H calculated for CI HITN 2 OBrF 2 requires 384.0405). Example 424 BF H 3 C 3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-l- (pyridin-4ylmethyl) pyridin-2 (IH) -one Step i. Preparation of 3-bromo-4-hydroxy-6-methyl-l-(pyridinCommercially available 4-hydroxy-6-methyl pyrone (I0 g, 79.3 mmol) was condensed with commercially available 4- (aminomethyl) pyridine (8 mL, 79.3 mmol) in water (50mL). The mixture was heated in an oil bath at reflux for 1 hour under nitrogen. The solvent was evaporated. MS and IH-NMR were consistent with the desired desbrominated structure. H-NMR (CD 3 OD, 400 MHz) 8 8.45 (dd, 2H, J= 1.6 Hz,!.6 Hz), 7.15 (d, 2H, J= 6.0 Hz), 6.00 (d, IH, J= 2.0 Hz), 5.80 (d, IH, J= 2.4 Hz) , 5.34 (s, 2H), 2.23 (s, 3H) ; ES-LRMS (M+H) m/z 217. To a suspension of the above compound (0.801 g, 3.7 mmol) in MeCI 2 (i0 mL) was added NBS (0.725 g, 4.07 mmol) . The reaction mixture stirred at room temperature for 30 minutes under nitrogen. The suspension was chilled in an ice bath and filtered. The solid was washed with fresh MeCI and dried to afford a beige solid (0.9663 g, 88%) after drying. IH-NMR (CD 3 OD, 400 MHz) 68.47 (d, 2H, J= 5.2 Hz), 7.16 (d, 2H, J= 6.0 Hz), 6.09 (s, IH), 5.40 (s, 2H), 2.24 (s, 3H) ; ES-LRMS (M+H) m/z 295/297. Step 2. Preparation of 3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6methyl-l- (pyridin-4-ylmethyl)pyridin-2 (IH) -one HaG To a cold solution of 2,4-difluorobenzylalcohol (0.569 mL, 5.1 mmol) in THF (5 mL) was added PPh 3 (resin, 2.55 g, 7.65 mmol) followed by the addition of DI (1.48 rnL, 7.65 mmol). The reaction mixture stirred at -10°C for 15 minutes under nitrogen. A solution of 3-bromo-4-hydroxy-6-methyl-1- (pyridin-4-ylmethyl)pyridin-2(1H)-one (1.0 g, 3.4 retool), in DMF (10 mL) was added to the resin suspension. The reaction mixture stirred at 0° C for 1.5 hours and then allowed to stir at room temperature overnight. The resin was filtered and rinsed with fresh MeOH and the filtrate was concentrated. The residue was dissolved in ethyl acetate and purified by flash column chromatography (ethyl acetate). The appropriate fractions were concentrated. IH-NMR (CD 3 OD, 400 MHz) 6 8.47 (d, 2H, J= 5.6 Hz), 7.63 (q, IH), 7.15 (d, IH, J= 5.6 Hz), 7.05 (m, 2H), 6.55 (s, IH), 5.45 (s, 2H), 5.31 (s, 2H) , 2.35 (s, 3H) ; ES-HRMS m/z 421.0366/423.0355 (M÷H calculated for C 19 HI N 2 0 2 F 2 Br requires 421.0358/423.0339). Example 428 er N H 3 C 3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyli- (pyridin-3ylmethyl ) pyridin2 (IH) -one Step I. Preparation of 3-bromo-4-hydroxy-6-methyl-l-(pyridin3-ylmethyl)pyridin-2(IH)-one OH Commercially available 4-hydroxyl-6-methyl pyrone (15 g, 119.0 mmol) was condensed with commercially available 3- (aminomethyl) pyridine (12.10 mL, 119.0 mmol) in water (75 mL). The mixture was heated in an oil bath at reflux for 1 hour under nitrogen. The solvent was evaporated. H-NMR (CD OD, 400 MHz) 6 8.43 (d, IH, J= 4.8 Hz), 8.38 (s, 1H), 7.60 (d, !H, J= 8.0 Hz) , 7.39 (dd, IH, J= 4.8 Hz, 4.8 Hz) , 5.97 (d, IH, J= 2.0 Hz), 5.79 (d, IH, J= 2.4 Hz), 5.33 (s, 2H), 2.28 (s, 3H) ; ES-LRMS (M+H) m/z 217. To a suspension of the above compound (5.01 g, 23.1 mmol in MeCI 2 (50 mL) was added NBS (4.53 g, 25.4 retool) . The reaction mixture stirred at room temperature for 30 minutes under nitrogen. The suspension was chilled in an ice bath and filtered. The solid was washed with fresh MeCI= and dried to afford a beige solid (7.89 g, 114%) after drying. ZH-NMR (CD OD, 400 MHz) 6 8.44 (d, IH, J= 4.4 Hz), 8.39 (s, IH), 7.62 (d, IH, J= 7.6 Hz), 7.39 (dd, IH, J= 5.2 Hz, 4.4 Hz), 6.07 (s, IH) , 5.39 (s, 2H) , 2.29 (s, 3H); ES-LRMS (M+H) m/z 295/297. Step 2. Preparation of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-l-(pyridin-3-ylmethyl)pyridin-2(IH)-one F F H 3 C The compound was prepared essentially as described in Step 2 of example 424 using 3-bromo~4-hydroxy-6-methyl-l-(pyridin-3ylmethyl)pyridin-2(iH)-one. ZH-NMR (CD 3 OD, 400 MHz) 6 8.45 (d, IH, J= 4.4 Hz) , 8.41 (s, IH) , 7.63 (m, 2H) , 7.41 (dd, IH, J= 5.2 Hz, 4.8 Hz), 7.02 (m, 2H), 6.52 (s, IH), 5.44 (s, 2H) , 5.29 (s, 2H), 2.40 (s, 3H); ES-HRMS m/z 421.0355/423.0358 (M+H calculated for C:gHz N 2 0 2 F 2 Br requires 421.0358/423.0339). Example 435 F\ B[ :N H 3 C 3-bromo-4- [(2,4-difluorobenzyl)oxy] -6-methyl-l- (pyridin-2ylmethyl) pyridin-2 (IH) -one Step i. Preparation of 3-bromo-4-hydroxy-6-methyl-l-(pyridin2-ylmethyl) pyridin-2 (IH) -one Commercially available 4-hydroxyl-6-methyl pyrone (5 g, 39.6 mmol) was condensed with commercially available 2- (aminomethyl) pyridine (4.03 niL, 39.6 mmol) in water (25 mL) . The mixture was heated in an oil bath at reflux for 1.5 hour under nitrogen. The solvent was evaporated. MS and H-NMR were consistent with the desired desbromonated structure. IHNMR (CD 3 OD, 400 MHz) 68.47 (d, IH, J= 4.8 Hz), 7.75 (ddd, IH, J= 2.0 Hz, 1.6 Hz, 1.6 Hz), 7.28 (dd, IH, J= 4.8 Hz, 4.8 Hz), 7.11(d, IH, J= 7.6 Hz), 5.98 (d, IH, J= 2.4 Hz), 5.77 (d, IH, J= 2.4 Hz), 5.35 (s, 2H), 2.28 (s, 3H); ES-LRMS (M+H) m/z 217. To a suspension of the above compound (3.0 g, 13.8 mmol) in MeCI 2 (30 mL) was added NBS (2.71 g, 15.18 mmol) . The reaction mixture stirred at room temperature for 2.5 hours under nitrogen. The suspension was chilled in an ice bath and filtered. The solid was washed with fresh MeCI 2 and dried to afford a beige solid (3.18 g, 77%) after drying. IH-NMR 3H) ; ES-LRMS (M+H) m/z 295/297. Step 2. Preparation of 3-bromo-4- [(2,4-difluorobenzyl)oxy] methyli- (pyridin-2-ylmethyl) pyridin-2 (IH) -one gr H 3 C The compound was prepared essentially as described in Step 2 of example 424 using 3-bromo-4-hydroxy-6-methyl-l- (pyridin-2-ylmethyl)pyridin-2(iH)-one IH-NMR (CD OD, 400 MHz) 8.45 (d, IH, J= 4.4 Hz), 7.76 (ddd, !H, J= 2.0 Hz, 2.0 Hz, Hz), 7.62 (q, IH), 7.29 (dd, IH, J= 5.2 Hz, 5.6 Hz), 7.21 IH, J= 8.0 Hz), 7.04 (m, 2H), 6.51 (s, IH), 5.45 (s, 2H), (s, 2H), 2.42 (s, 3H) ; ES-HRMS m/z 421.0354/423.0332 (M+H calculated for C 19 HI N 2 0 2 F 2 Br requires 421. 0358/423. 0339). Examples 425-427, 429-435, 436-437 The following compounds were prepared essentially according to the procedures set forth above for Example 424, using the products of Step 1 of Examples 424, 428, or 435. Ex. No. RI R 2 R 3 R 4 Rs X Y Z MF M+H m/z ES-HRMS required m/z I 425 H H F H H N CH CH CIgHIGN 2 0 2 FBr 403.0452/ 403. 044L 405. 0434 4O5. 041 426 F H F H F N CH CH C 19 HI 4 N 2 0 2 F Br 439.0264/ 439.027 441.0245 441. 027z 427 F H H H F N CH CH C 19 HIsN 2 0 2 F 2 Br 421.0358/ 421.0371 423 . 0339 423.036[ 429 H H F H H CH N CH C 19 HI 6 N O 2 FBr 403.0487/ 403.048: 405.0438 405.043[ 430 F H F H F CH N CH C 19 HI 4 N 2 0 2 F 3 Br 439.0264/ 439.026" 441. 0245 441.024] 431 F H H H H CH N CH C 19 HI N 2 0 2 FBr 403.0452/ 403.048f 405. 0434 4O5.0474 432 F H F F H CH N CH C 19 HI 4 N 2 0 2 F 3 Br 439.o264/ 439.026( 441. 0245 441.023] 433 F H C1 H H CH N CH CIgHIsN 2 0 2 FCIBr 437.0062/ 437.006[ 439. 0041 439.004] 434 C1 H F H H CH N CH C 19 HIsN 2 0 2 FCIBr 437.0062/ 437.004[ 439.0041 439.004435 F H H H F CH N CH C 19 HIsN 2 0 2 F 2 Br 421.0358/ 421.037: 423. 0339 423.033( 436 H H F H H CH CH N CIgHI 6 N 2 0 2 FBr 403.0452/ 403. 045< 405. 0434 405.037! 437 F H F H F CH CH N C 19 HI 4 N 2 0 2 F 3 Br 439.0264/ 439.026{ 441. 0245 441.024: 438 F H F F H CH CH N C 19 HI 4 N 2 0 2 F 3 Br 439. 0264/ 439. 026 441. 0245 441 . 024 NMR characterization of compounds of Examples 425-427, 429435, 436-437 Ex.No. NMR Data Example 439 CH 3-bromo-4- [2- (4fluorophenyl) ethyl] 3-ylmethyl)'pyridin-2 Step I. Preparation of 3-bromo-6-methyl-2-oxo-l-(pyridin-3ylmethyl)-l,2-dihydropyridin-4-yl trifluoromethanesulfonate O /CF 3 o,S,o H 3 C r To a chilled suspension (-30° C) of 3-bromo-4-hydroxy-6methyl-l- (pyridin-3-ylmethyl)pyridin-2 (IH) -one (0.48!g, 1.63 mmol] in dichloromethane (6 mL) was added triethylamine (0.28 mL, 2.04 mmol), followed by the addition of a solution of trifluoromethanesulfonic anhydride (0.4 mL, 2.44 mmol) in dichloromethane (3 m L) . The reaction mixture stirred at -30° C under nitrogen for 1 hour. The reaction mixture was diluted with dichloromethane and washed with cold NaHCO 3 /water. The organic extracts were dried over Na 2 S0 4 and the filtrate was concentrated under reduced pressure to afford the desired compound as a yellow semisolid (0.6675 g, 95%) after drying. ES-LRMS (M+H) m/z 427.1/429.1. Step 2. Preparation of 3-bromo-4-[(4-fluorophenyl)ethynyl]-6~ methyl-l-(pyridin-3-ylmethyl)pyridin-2(IH)-one ar F H 3 C TO a degassed solution of 3-bromo-6-methyl-2-oxo-l- (pyridin-3-ylmethyl)-l,2-dihydropyridin-4-yl trifluoromethanesulfonate (0.6675 g, 1.56 mmol) in DMF (9 mL), DIEA (0.35 mL, 2.03 mmol), 4-fluorophenylacetylene (0.235 mL, 1.95 mmol) and PdCl 2 (PPh 3 ) 2 (0.11g) were added. The reaction mixture stirred at room temperature under nitrogen for 1 hour and then heated in an oil bath (65°C) under nitrogen overnight. The solvents were distilled in vacuo and the residue was purified by flash column chromatography (5% methanol in ethyl acetate). The extracts were concentrated to afford the desired compound (0.432 g, 69%) after drying. :HN-MR (CD 3 OD, 400 MHz) 6 8.45 (s, 2H), 7.96 (s, IH), 7.64 (m, 3H), 7.41 (dd, IH, J= 4.8 Hz, 4.8 Hz), 7.18 (t, 2H, J= 8.8 Hz), 6.46 (s, IH) , 5.45 (s, 2H), 2.37 (s, 3H) ; ES-HRMS m/z 397.0361/399.0310 (M+H calculated for C 20 HIsN 2 OFBr requires 397.0346/399.0328). Step 3. Preparation of 3-bromo-4- [2-(4-fluorophenyl)ethyl]-6methyl-l-(pyridin-3-ylmethyl)pyridin-2(1H)-one ar F H 3 C A suspension of 3-bromo-4- [(4-fluorophenyl)ethynyl]-6methyl-l-(pyridin-3-ylmethyl)pyridin-2(iH)-one (0.430 g, 1.01 t mmol) in Ethyl acetate (5 mL) and EtOH (5 mL), containing PtO (0.015 g) was stirred in an atmosphere of hydrogen (15 psi) in a FischerPorter bottle for 2 hours. The reaction mixture was filtered and the filtrate was concentrated to reduce volume. The material was purified by flash column chromatography (ethyl acetate). The appropriate fractions were combined and concentrated under reduced pressure to afford the desired product (0.0943 g, 22 %) as a sticky semisolid after drying. IH-NMR (CD 3 OD, 400 MHz) 6 8.46 (d, IH) , 5.43 (s, 2H), 2.93 (m, 4H), 2.31 (s, 3H) ; ES-HRMS m/z 401.0645/403.0603 (M+H calculated for C 20 HIgNzOFBr requires 401.0659/403.0641) . Example 440 F--. H 3 C 3-bromo-4- [2- (4 - fluorophenyl) ethyl] ~ 6-methylI- (pyridin4-ylmethyl)pyridin-2(iH)-one The title compound was prepared by a procedure similar to the one described for step 1 to step3 (0.374 g, 25%). MS and IH-NMR for step 1 were consistent with the desired structure. IH-NMR (CD OD, 400 MHz) 6 8.80 (d, 2H, J= 6.8 Hz), 7.89 (d, 2H, J= 6.8 Hz), 6.61 (s, IH) , 5.66 (s, 2H), 2.45 (s, 3H) ; ES-HRMS m/z 427.9645/429.9625 (M+H calculated for CI HIIN 2 0 4 SF 3 Br requires 427.9599/429.9578). MS and IH-NMR for step 3 were consistent with the desired structure. H-NMR (CD 3 OD, 400 MHz) 8 8.48 (d, 2H, J= 5.2 Hz), 7.21 (m, 2H), 7.13 (d, 2H, J= 5.2 Hz), 6.98 (t, 2H, J= 9.0 Hz), 6.26 (s, IH), 5.43 (s, 2H), 2.95 (m, 4H), 2.25 (s, 3H); ES-HRMS m/z 401.0682/403.0636 (M+H calculated for C 20 HIgN OFBr requires 401.0659/403.0641). Example 441 3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-(pyridin3-ylmethyl)pyridin-2(!H)-one Step I. Preparation of 3-chloro-4-hydroxy-6-methyl-l- (pyridin-3-ylmethyl)pyridin-2(iH)-one OH H 3 C I To a suspension of 4-hydroxyl-6-methyl-l- (pyridin-3ylmethyl)pyridin-2(iH)-one (1.016 g, 4.7 mmol) in MeCI 2 (i0 mL) was added NCS (1.21 g, 1.78 mmol) . The reaction mixture stirred at room temperature for 24 hours under nitrogen. The suspension was chilled in an ice bath and filtered. The solid was washed with fresh MeCI 2 and dried to afford a yellow solid (I.00 g, 85%) after drying. IH-NMR (CD OD, 400 MHz) 6 8.54 (m, 2H), 7.85 (d, IH, J=l.6 Hz), 7.61 (m, IH), 6.10 (s, IH), 5.41 (s, 2H), 2.33 (s, 3H) ; ES-LRMS (M+H) m/z 251/253. Step 2. Preparation of 3-chloro-4-[(2,4-difluorobenzyl)oxy]- To a degassed cold solution of DMF (i0 mL) and ?Pha (resin, 2.2 g, 6.6 retool) was added DEAD (1.038 mL, 6.6 mmo!) . The reaction mixture stirred at -I0° C for 20 minutes under nitrogen. A solution of 3-chloro-4-hydroxy-6-methyl-l- (pyridin-3-ylmethyl)pyridin-2(IH)-one (i.00 g, 4.0 retool) and 2,4-difluorobenzylalcohol (0.66 mL, 6.0 mmol) in DMF (I0 mL) was added to the resin suspension. The reaction mixture stirred at -i0° C for 30 minutes and then allowed to stir at room temperature for 1 hour. The resin was filtered and rinsed with fresh MeOH and the filtrate concentrated. The residue was dissolved in ethyl acetate and purified by flash column chromatography (5% methanol in ethyl acetate). The appropriate fractions were concentrated. H-NMR (CDaOD, 400 MHz) 6 8.45 (ddd, 2H, J= 1.6Hz, 1.6 Hz, 1.6 Hz), 7.61 (m, 2H), 7.41 (dd, IH, J= 4.4 Hz, 4.8 Hz) , 7.02 (m, 2H) , 6.55 (s, IH) , 5.43 (s, 2H), 5.29 (s, 2}{), 2.41 (s, 3H) ; ES-HRMS m/z 377.0882/379.0840 (M+H calculated for C 19 HI N 2 0 2 F 2 CI requires 377.0863/379.0840) . Example 442 F. F Br / H 2 N TFA l-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-bromo-6methyl-4-[(2,4,6-trifluorobenzyl)oxy]pyridin-2(iH)-one trifluoroacetate The title compound was prepared by a procedure similar to the one described for Example 385, step 2 (0.142 g, 9%). IH ES-HRMS m/z 469.0488/471.0464 (M+H calculated for C 19 HIvN 4 0 2 F 3 requires 469. 0481/471.0463) . Example 443 HN TFA 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-{ [2-methyl-4- (methylamino)pyrimidin-5-yl]methyl}pyridin-2(iH)-one trifluoroacetate To a solution of l-[(4-amino-2-methylpyrimidin-5yl)methyl]-3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(iH)-one hydrochloride (0.15 g, 0.3 mmol) in DMF (3 mL) was added DBU (0.09 mL, 0.6 mmol). The solution was cooled in an ice bath and iodomethane (0.019 mL, 0.3 mmol) was added. The reaction mixture stirred at room temperature under nitrogen for 2 hours. The reaction was purified by reverse phase HPLC 10-90% CH3CN/water (30 minute gradient) at a flow rate of i00 mL/min. The appropriate fractions (m/z= 465 M+H) were combined and freeze dried to afford the desired product (0.035 g, 25%) as a white powder. IH NMR (CD 3 OD, 400 MHz) 6 7.72 (s, IH), 7.60 (m, IH), 7.03 (m, 2H), 6.62 (s, IH), 5.31 (s, 2H) , 5.16 (s, 2H), 3.77 (s, 3H), 2.60 (s, 3H), 2.47 (s, 3H) ; ES-HRMS m/z 465.0717/467.0712 (M+H calculated for C 20 H 20 N 4 0 2 F 2 Br requires 465.0732/467.0714). Example 444 ethyl N_(5_{ [ 3 -br 0 m 0 -4-[(2,4-difluor 0 benzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}-2-methylpyrimidin-4-yl)glycinate trifluoroacetate The title compound was prepared by a procedure similar to the one described for Example 442 with the exception that the reaction mixture had to be heated at oil bath temperature 70° C for 2 days (0.1384 g, 51%). ZH NMR (CD 3 OD, 400 MHz) 6 7.78 (s, IH), 7.61 (m, IH), 7.03 (m, 2H), 6.61 (s, IH), 5.30 (s, 2H), 5.18 (s, 2H), 5.03 (s, 2H), 4.27 (q, 2H), 2.55 (s, 3H), 2.46 (s, 3H) , 1.28 (t, 3H, J= 7.0 Hz) ; ES-HRMS m/z 537.0936/539.0932 (M+H calculated for C 23 H 24 N 4 0 4 F 2 Br requires 537.0943/539.0926) . Example 445 F F CI HN "-OH N-(5-{ [3-chloro-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}-2-methylpyrimidin-4-yl)- 2-hydroxyacetamide trifluoroacetate To a chilled solution of l-[(4-amino-2-methylpyrimidin-5yl)methyl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(iH)-one trifluoroacetate (0.200 g, 0.38 mmol) in DMF (20 mL) and a catalytic amount of DMAP was added triethylamine (0.064 mL, 0.38 mmol). The reaction stirred at - 20° C and acetoxyacetyl chloride (0.082 mL, 0.76 mmol) was added. The reaction stirred cold for 15 minutes and then allowed to warm up to room temperature for 3 hours. The reaction was monitored by LR-ESMS m/z = 466. The reaction was incomlete after 3 hours. Added acetoxyacetyl chloride (0.05 mL, 0.466 mmol), and triethylamine (0.2 mL, 1.43 mmol) to the reaction mixture and continued to stir overnight at room temperature. The next morning the reaction heated at 65° C for 3 hours. The solvent was removed in vacuo and IN LiOH (2.5 mL) was added to the residue. The reaction was heated at 60° C for 5 hours. The reaction was diluted with acetonitrile and water (i:i) and purified by reverse phase HPLC in 10-90% CH 3 CN/water (30 minute gradient) at a flow rate of 50 mL/min. The appropriate fractions were freeze dried to afford the desired product (0.020 g, 9%). IH NMR (CD 3 OD, 400 MHz) 6 8.04 (s, IH), 7.6 (m, IH), 7.02 (m, IH), 6.59 (s, IH), 5.30 (s, 2H), 5.24 (s, 2H), 4.26 (s, IH), 2.60 (s, 3H), 2.43 (s, 3H) ; ES-HRMS m/z 465.1161 (M+H calculated for CnH 20 N 4 0 4 F 2 CI requires 465.1136). Example 446 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-l- [ (5methylpyrazin2 -yl ) methyl ] pyridin2 (IH) - one Step I. Preparation of 3-chloro-4-hydroxy-6-methyl-l- [(5methylpyrazin-2-yl) methyl] pyridin-2 (IH) -one To a solution of 4-hydroxy-6-methyl-l-[(5-methylpyrazin2-yl)methyl]pyridin-2(IH)-one (l.00g, 4.3 retool) in glacial acetic acid (I0 mL) was added NCS (0.79 g, 5.94 mmol) . The reaction mixture stirred at 60° C for 6 hours. The solvent was removed under reduced pressure and the resulting residue was triturated with ethyl acetate. The desired product was filtered and dried (0.80 g, 69%). IH NMR (CD OD, 400 MHz) 6 8.47 (s, IH) , 8.42 (s, IH) , 6.08 (s, IH) , 5.36 (s, 2H), 2.50 (s, 3H) , 2.43 (s, 3H) ; ES-HRMS m/z 266.0691 (M+H calculated for C 12 HI 3 N 3 0 2 CI requires 266. 0691) . Step 2. Preparation of 3-chloro-4-[(2,4-difluorobenzyl)oxy]- 6-methyl-l- [(5-methylpyrazin-2-yl)methyl]pyridin-2(IH)-one To a solution of 3-chloro-4-hydroxy-6-methyl-l-[(5methylpyrazin-2-yl)methyl]pyridin-2(1H)-one (2.48 g, 9.3 mmol) in DMA (7 mL)was added K 2 CO 3 (1.54 g, II.0 mmol) followed by 2,4-difluorobenzyl bromide (1.2 mL, 9.3 mmol) . The reaction mixture stirred at room temperature under nitrogen for 1.5 hours. The solvent was distilled in vacuo. The resulting residue was diluted in dichloromethane and washed with water. The organic extracts were concentrated and the resulting residue was purified by flash column chromatography (ethyl acetate). The appropriate fractions were combined, and concentrated. IH NMR (CD 3 OD, 400 MHz) 6 8.49 (d, IH, J=l.2 HRMS m/z 392.1014 (M+H calculated for C gHITN 3 0=CIF 2 requires 392.0972). Example 447 TFA 3-br 0 m 04-[(2,4-diflu 0 r 0 benzyl) 0 xy]-6-methyl-l-({5- [(methylamino)methyl]pyrazin-2-yl}methyl)pyridin-2(IH)-one trifluoroacetate To a suspension of 3-bromo-l-{[5-(chloromethyl)pyrazin-2yl]methyl}-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(iH)- one (0.25 g, 0.53 mmol) in THF was added methylamine (i mL, 2.1 mmol) . The reaction was sealed and stirred at room temperature overnight. The reaction mixture was diluted in water:acetonitrile (i:I) and purified by reverse phase HPLC 10-90% CH 3 CN/water (30 minute gradient) at a flow rate of mL/min. The appropriate fractions were combined and freeze dried to afford the desired product (0.22 g, 71%) as an amorphous solid, iN NMR (CD 3 OD, 400 MHz) 6 8.73 (s, IH), 8.55 (s, IH), 7.6 (m, 2H), 7.02 (m, IH), 6.54 (s, IN), 5.47 (s, 2H), 5.29 (s, 2 H), 4.37 (s, 2 H), 2.78 (s, 3H), 2.56 (s, 3H) . ES-HRMS m/z 465.0732/467.0709 (M+H calculated for C 0 H 20 N 4 0 2 BrF requires 465.0732/467.0714). Example 448 F oJ 0.. Ethyl 5-{ [3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl2-oxopyridin-l(2H)- yl]methyl}pyrazine-2-carboxylate To a mixture of 3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one (0.59 g, 2.07 mmol) and ethyl 5-(bromomethyl)pyrazine-2-carboxylate (0.62 g, 2.4 mmol) in THF (15 mL) was added NaH (0.06 g, 2.4 mmol) . The reaction stirred at 60° C for 3.5 hours. The solvent was removed under reduced pressure and the residue was partitioned over dichloromethane and citric acid (5%). The organic extracts were washed with water and dried over Na 2 SO 4 (anhydrous). The organic extracts were concentrated and the residue was purified by flash column chromatography (i00 % ethyl acetate). The appropriate fractions were combined and concentrated under reduced pressure to remove solvent. IH NMR (CD 3 OD, 400 MHz) 6 9.11 (d, IH, J= 1.6 Hz), 8.77 (s, IH), 7.52 (m, IH), 7.02 (m, 2H), 6.57 (s, IH), 5.53 (s, 2H), 5.30 (s, 2H), 4.49 (q, 2H), 2.52 (s, 3H), 1.39 (t, 3H, J= 7.2 Hz) ; ESHRMS m/z 450.1045 (M+H calculated for C 2 HIgN 3 0 4 CIF 2 requires 450.01027). Example 449 (hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(IH)-one To a suspension of ethyl 5-{ [3-chloro-4-[(2,4difiuorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}pyrazine-2-carboxylate (4.0 g, 8.9 mmol) in THF:tbutanol (I:i) (i0 mL) was added NaBH 4 (0.46 g, 12.4 mmol) . The reaction stirred at room temperature under argon overnight. The reaction mixture was quenched with acetic acid [2 mL) and the solvent was removed in vacuo. The residue was triturated with water and filtered. The solid was washed with fresh water followed by ethanol. The solid was purified by flash column chromatography (100% ethyl acetate). The appropriate fractions were combined and concentrated under reduced pressure to afford the desired compound (1.58 g, 44%) as a white solid. IH NMR (CD 3 OD, 400 MHz) 6 8.59 (s, IH), 8.56 (s, IH), 7.52 (m, IH), 7.01 (m, 2H), 6.55 (m, IH), 5.45 (s, 2H), 5.29 (s, 2H), 4.71 (2H), 2.54 (s, 3H); ES-HRMS m/z 408.0940 (M+H calculated for C 19 HI N 3 0 CIF 2 requires 408.0921). Example 450 l(2H)-yl]methyl}-N,N-dime<hy!pyrazine-2-carboxamide To a cold solution of 5-{ [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin~l(2H)- yl]methyl}pyrazine-2-carboxylic acid (0.175 g, 0.37 mmo!) in DMF (5 mL, -I0° C) was added IBCF (0.046 mL, 0.35 mmol) followed by NMM (0.041 mL 0.37 mmol) . The reaction was activated for 20 minutes at -15° C after which dimethylamine (0.375 mL, 0.74 mmol) was added. The reaction stirred at -i0° C to room temperature for 45 minutes. The solvent was removed in vacuo and the residue was purified by reverse phase HPLC 10-90% CH 3 CN/water (30 minute gradient) at a flow rate of mL/min. The appropriate fractions were combined and freeze dried to afford the desired product (0.140g, 75%) as a white solid. IH NMR (CD 3 OD, 400 MHz) 6 8.68 (s, IH) , 8.67 (s, IH) , 7.52 (m, IH) , 7.02 (m, 2H), 6.54 (s, IH) , 5.50 [s, 2H), 5.30 (s, 2H), 3.11 (s, 3 H), 3.07 (s, 3H), 2.55 (s, 3H) ; ES-HRMS m/z 493.0680/495.0657 (M+H calculated for CnH 20 N 4 0 3 BrF 2 requires 493.0680/495.0657). Example 451 HN O 5- { [3 -bromo-4- [ (2,4-difluorobenzyl ] oxy] -6-methyl-2-oxopyridin1 (2H) -yl] methyl } -N-methylpyrazine2 - carboxamide The title compound was prepared essentially as in Ex. 450, substituting dimethylamine with methylamine. IH NMR (CD 3 OD, 400 (s, 3H); ES-HRMS m/z 479.0542/481.0518 (M+H calculated for C 0 HIsN 4 0 BrF 2 requires 479.0525, 481.0507). Example 452 0 IIOH Br-/K' N N 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -I- { [5- (l-hydroxy-lmethylethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(IH)-one To a cold flask of MeMgBr (1.59 mL, 1.0 mmol) was added a suspension of ethyl 5-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}pyrazine-2-carboxylate (0.5 g, 1.0 mmol) in THF (20 mL). The reaction stirred at 0 C for 1.5 hours and then at room temperature overnight. The reaction was quenched with cold citric acid (25 mL, 5%) and extracted with ethyl acetate (2 X i00 mL). The organic extracts were washed with fresh water. The organic extracts were concentrated and purified by reverse phase HPLC 10-90% CH 3 CN/water (30 minute gradient) at a flow rate of 70 mL/min. The appropriate fractions were combined and freeze dried to afford the desired product (29.9 rag, 6%). IH NMR (CD 3 OD, 400 MHz) 6 8.76 (d, IH, J= 1.6 Hz), 8.54 (d, IH, J= 1.2 Hz), 7.52 (m, IH), 7.02 (m, 2H), 6.52 (s, IH), 5.45 (s, 2H), 5.29 (s, 2H) , 2.55 (s, 3H) , 1.52 (s, 6H) ; ES-HRMS m/z 480. 0745/482.0722 (M+H calculated for C 21 HnN 3 0 3 BrF 2 requires Example 453 O. 8r I 5- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methy!-2-oxopyridin1 (2H) -yl] methyl } -N- (2-methoxyethyl) pyrazine2-carboxamide The title compound was prepared essentially as in Ex. 450, substituting dimethylamine with 2-methoxyethylamine. H NMR (CD 3 OD, 400 MHz) 6 9.08 (d, IH, J= 1.2 Hz), 8.70 (d, IH, J= Hz), 7.61 (m, IH), 7.04 (m, 2H), 6.54 (s, IH), 5.53 (s, 2H), 5.30 (s, 2H), 3.56 (m , 4H), 3.30 (s, 3H), 2.54 (s, 3H) ; HRMS m/z 523.0822/525.0810 (M+H calculated for C 22 H 22 N 4 0 4 BrF requires 523.0787/525.0770) . Example 454 O N O 3 -bromo-4- [ (2,4 -difluorobenzyl) oxy] -6-methyl-!- { [5- (morpholin4-ylcarbonyl) pyrazin-2-yl ] methyl }pyridin-2 (1H) -one The title compound was prepared essentially as in Ex. 450, substituting dimethylamine with morpholine. IH NMR 3H) ; ES-HRMS m/z 535.0816/537.0817 (M+H calculated for C 2 H 22 N 4 0 4 BrF 2 requires 535. 0787/537. 0770) . Example 455 OH 3-chloro-4- [(2,4-difluorobenzyl)oxy]-l-({5-[(4hydroxypiperidin-l-yl)carbonyl]pyrazin-2-yl}methyl)-6methylpyridin-2(iH)-one Step I. Preparation of 5-{[3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}pyrazine-2-carboxylic acid HO O, O A mixture of ethyl 5-{ [3-chloro-4- [ (2,4di f luorobenzyl ) oxy] - 6 -methyl - 2 -oxopyridin1 (2H) - yl]methyl}pyrazine-2-carboxylate (l.03g, 2.3 mmol) in IN NaOH (3.4 ml, 3.45 mmol, EtOH/water I:I v/v) stirred at room temperature for 2 hours. The reaction mixture was quenched with 5% citric acid and filtered. The solid was washed with water and dried to afford the desired product (i.011 g, 100%) as a white solid, iH NMR (CD 3 OD, 400 MHz) 6 9.02 (s, IH), (s, 2H), 5.30 (s, 2H), 2.52 (s, 3H) ; ES-HRMS m/z 422.0732 (M+H calculated for C 19 HIsN 3 0 CIF requires 422.0714). Step 2. Preparation of 3-chloro-4-[(2,4-difluorobenzyi)oxy]- l-({5-[(4-hydroxypiperidin-l-yl)carbonyl]pyrazin-2-y!}methy!)- 6-methylpyridin-2(iH)-one The title compound was prepared by a procedure similar to the one described for Example 453 (0.1396 g, 47%). IH NMR (CD 3 OD, 400 MHz) 6 8.67 (s, 2H), 7.59 (m, IH), 7.02 (m, 2H), 6.57 (s, IH), 5.49 (s, 2H), 5.30 (s, 2H), 4.16 (m, IH), 3.89 (septet, IH), 3.72 (m, IH), 3.38 (m, 2H), 2.56 (s, 3H), 1.93 (m, IH), 1.83 (m, IH), 1.45 (m, 2H) ; ES-HRMS m/z 505.1485 (M+H calculated for C 2 H 24 N 4 0 4 CIF 2 requires 505.1449). Example 456 F F NH ''/0 H 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl] methyl } -N- (3 -hydroxy~ 2,2 - dimethylpropyl ) pyra z ine2 - carboxamide The title compound was prepared by a procedure similar to the one described for Example 455 (0.215 g, 71%). IH NMR (CDBOD, 400 MHz) 6 9.08 (d, IH, J= 1.2 Hz) , 8.71 (d, IH, J= 1.6 Hz), 7.58 (m, IH), 7.02 (m, 2H), 6.57 (s, IH) , 5.52 (s, IH), 5.30 (s, IH) , 3.31 (s, 4H), 2.55 (s, 3H), 0.912 (s, 6H) ; ESHRMS m/z 507.1630 (M+H calculated for C 24 H 2 N 4 0 4 CIF 2 requires Example 457 O 5-{[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}-N-(2,2,2-trifluoroethyl)pyrazine2-carboxamide The title compound was prepared by a procedure similar to the one described for Example 455 except no purification was required, only a NaHCO 3 /ethyl acetate extraction was needed (0.2176 g, 73%). IH NMR (CD 3 OD, 400 MHz) 6 9.11 (d, IH, J= 1.6Hz) , 8.73 (d, IH, J= 1.3 Hz), 7.59 (m, IH), 7.02 (m, 2H), 6.57 (s, IH), 5.53 (s, 2H), 5.30 (s, 2H), 4.01 (q, 2H), 2.54 (s, 3H); ES-HRMS m/z 503.0930 (M+H calculated for C 21 HIvN 4 0 3 CIFs requires 503.0904). Example 458 F Broth l-allyl-3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin2 (IH) -one Step i: l-allyl-4-hydroxy-6-methylpyridin-2(iH)-one. 4hydroxy-6-methyl-2-pyrone (2g, 16 mmol) was stirred in water (25 mL) . Allylamine (1.2 ml, 16mmol) was added to the reaction. The reaction was then heated to i00 °C at which point the reaction became homogeneous. The reaction was stirred at I00 °C for 2h. The reaction was then allowed to cool to rt after which a white precipitate formed. The precipitate was isolated by suction filtration. After additional washing with water, 1.8g (69%) of an off-white solid was obtained. Step 2: 1-allyl-4-[(2,4-difluorobenzy!)oxy]-6-methylpyridin- 2(iH)-one. To a stirred solution of the above pyrone(4.0g, 24 mmol) in DMF(75ml) was added Cs 2 CO 3 (7.8g, 24mmol) fo!lowed by addition of 2,4-diflurorbenzyl bromide(3.4 mmol, 26.4 mmol) . The resulting mixture was stirred at rt for 2h. Additional Cs 2 CO 3 (ig) and bromide (i ml) was added and the reaction was stirred for an additional 2h. The Cs 2 C0 3 was removed by suction filtration. The DMF was removed under vacuum and the crude material was purified by flash chromatography. Elution with ethyl acetate-hexanes (2:1 to I:I) afforded 1.5 g (21%) of the desired compound. Step 3: l-allyl-3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6methylpyridin-2 (IH)-one. To a stirred suspension of the above pyridinone (ig, 3.4 mmol) in CH 3 CN (I0 ml) was added nbromosuccinimide (670 mg, 3.8 mmol). The reaction mixture was stirred, at rt, for 3h. The product was obtained by filtration of the reaction mixture and washing of the solid with diethyl ether. IH-NMR (DMSOdJ400 MHz) 6 7.62 (app q, J = l13.66(quar, J = IH) ; HRMS m/z 370.0255 (M + Hcalcd for C 16 HIsBrF 2 N0 2 = 370.0246). Example 459 F cIO l-allyl-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin2 (IH) -one Step I: l-allyl-3-chloro-4-hydroxy-6-methylpyridin-2(iH)-one. To a stirred solution of l-allyl-4-hydroxy-6-methylpyridin2(IH)-one (500 mg, 3.0 mmol) in CH 3 CN(10 ml), at rt, was added sequentially n-bromosuccinimide (440 mg, 3.3 mmol) and dichloroacetic acid (546 NI, 6.62 mmol) . The resulting mixture was stirred for 2h. The heterogeneous mixture was filtered and the solid was washed with additional CHAIN to give 350 mg (59%) of the desired product as a tan solid. IH-NMR (DMSOad300 MHz) 6 11.16 (s, IH), 5.98-5.86 (m, 2H), 5.12 (dd, J = 10.5, 1.5 Hz, IH), 4.89 (dd, J = 17.1, 1.5 Hz, IH) 4.63-4.61 (m, 2H), 2.29 (s, 3H). ES-HRMS m/z 200.050 (M + H calcd for CgHIICINO 2 = 200.0470) Step 2: l-allyl-3-chloro-4- [ (2,4-difluorobenzyl oxy}-6methylpyridin-2(IH)-one. The title compound was prepared by the procedure outline in the synthesis of Example 458, step 3. 4.67 (m, 2H), 2.41 (s, 3H) . ES-HRMS m/z 326.0760 (M + H calcd for CI HIsCIF 2 N0 2 = 326.0790) . Example 460 o 0 Methyl (2E)-4- [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin1 (2H) -yl] but-2-enoate To a stirred suspension of NaH (277 mg, II mmol) in anhydrous THF (30 ml), which was cooled to 0°C, was slowly added 3-bromo4- [ (2,4-dif!uorobenzy!)oxy] -6-methylpyridin-2(IH)-one (3.3g, i0 mmol). The resulting slurry was stirred for 15 min, after which methyl 4-bromocrotonate (1.4 ml, 12 mmol) was added to the reaction. The ice bath was removed and the reaction was heated to reflux for 16h. The reaction was quenched by the addition of IN NH 4 CI. The layers were separated and the aqueous layer was extracted with CH 2 C1 2 (5x). The organics were combined, dried, and concentrated in vacuo. The crude yellowish material was then triturated with Et 2 0 to give, after filtration and drying, 1.8g (43%) of a white solid. IH-NMR (DMSO /300 MHz) 6 7.65 (app q, J = 8.7 hz, IH), 7.36 (app dr, J = 12.0, 3.0 hz, IH) ; 7.17 (dt, J = 8.4, 1.8 Hz, IH) ; 6.94 (dt, J = 15.9, 4.5 Hz, IH) ; 6.57 (s, IH), 5.52 (d, J = 15.9 Hz, IH), 5.29 (s, 2H), 4.84 (m, 2H), 3.63 (s, 3H) , 2.33 (s, 3H) . ES-HRMS m/z 428.0301 (M + H calcd for C 18 HITBrF 2 N0 4 = Example 461 O 3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-l-prop-2ynylpyridin-2(iH)-one. Stepl: 4- [(2,4-difluorobenzyl)oxy]-6-methyl-l-prop-2ynylpyridin-2(iH)-one. The title compound was prepared by alkylation of 4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin- 2(IH)-one (2.5g, I0 mmol) with propargyl bromide (1.3 ml, ii.0 mmol) as described above to give 1.3g (44%) of the desired product. IHNMR (DMSO 6 /300 MHz) 6 7.60 (app q, J = 8.4 hz, IH) , 7.35-7.27 (m, IH) ; 7.16-7.10 (m, IH) ; 5.94 (d, J = 2.1 Hz, IH), 5.88 (d, J = 3.0 Hz, IH), 5.03 (s, 2H), 4.76 (d, J 2.4, Hz, 2H) , 3,31 (s, 3H), 3.24 (t, J = 2.4 Hz, IH), 2.39 (s, 3H) ; ES-HRMS m/z 290.0994 (M + H calcd for C 16 HI 4 F 2 NO 2 = 290.0993). Step 2: Bromination of 4-[(2,4-difluorobenzyl)oxy]-6-methyl-l- prop-2-ynylpyridin-2(iH)-one (500 rag, 1.67 mmol) with NBS (300 mg, 1.67 mmol) was carried out in the manner described above to give 350 mg (57%) of the desired compound. IH-NMR (DMSOdJ300 MHz) 6 7.67 (app q, J = 9.0 hz, IH), 7.36 (app dt, J = 10.5, 2.4 hz, IH) ; 7.23-7.16 (m, IH) ; 6.60 (s, IH), 5.29 (s, 2H] , 4.90 (d, J = 2.4, Hz, IH) , 3.35 (s, 3H), 3.32 (s, IH), 2.53 (s, 3H) ; ES-HRMS m/z 368.0107 (M + H calcd for Example 462 F... OH 4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-!-(pyridin3-y!methyl)pyridin-2(iH)-one. Stepl: To a suspension of (4-[(2,4-difluorobenzyl)oxy]- 6-methyl-l-(pyridin-3-ylmethyl)pyridin-2(iH)-one) (710 mg, 2 mmol) in dioxane (i0 mL) was added selenium dioxide (1.1g I0 mmol) . The resulting mixture was heated to 160 °C in a 125 nil sealed tube for lb. The reaction was filtered through a fritted funnel. The filtrate was washed with (i0:i) CH 2 CI 2 - MeOH. The organics were combined and concentrated in vacuo. The crude material was purified by flash chromatography. Elution with (50:50 - 0:100)hexanes yielded 450 mg (63%) of the aldehyde. IH-NMR (DMSOd /400 MHz). 69.48 (s, IH, CHO) . Step 2: The aldehyde (350 mg, 1 mmol) was dissolved in MeOH (4 mL) and cooled to 0 °C To this mixture was added NaBH 4 (28 mg, 1 mmol) in one portion. After 30 min, additional NaBH4 (20 mg) was added to the reaction. The MeOH was then removed under vacuum. The residue was diluted with IN NH 4 CI and then extracted with CH 2 CI 2 (4X) . The organics were combined, dried, and concentrated in vacuo. The yellowish crude product was then taken up in (i:i) CH 2 CI 2 -Et 2 0. After sitting for a period of time a white precipitate resulted. Filtration and washing with additional Et 2 0 yielded, after drying, 250 mg (55%) of the desired alcohol. IH-NMR (DMSOd 6 /400 MHz). 58.42 (dd, J = 4.4, 2H). LC/MS, tr = 1.19 minutes (5 to 95% acetonitrile/water minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 359.1 (M+H) Example 463 OH N O 3-Bromo-4- [ (2,4-difluorobenzyl) oxy] -6- (hydroxymethyl) (pyridin3-ylmethyl) pyridin-2 (IH) -one. The title compound was prepared by bromination of as described above to give a 60% yield. IH-NMR (DMSOd 6 /300 MHz). 6 7.93 (d, J = 7.8 Hz, IH), 7.73-7.65 (m, 3H), 7.38 (dt, J 10.2, 2.4 Hz, IH), 7.21 (app t, J = 8.7 Hz, 2H), 6.74 (s, IH), 5.38.-5.36 (m, 4H), 4.50 (s, 2H) ; ES-HRMS m/z 437.0311 (M + cacld for C 19 HI 6 BrF 2 N 2 0 2 = 437.0313). Example 464 [(dimethylamino)methy!]-l-(pyridin-3-ylmethyl)pyridin-2(iH)- one. The title compound was prepared in a similar manner to the procedure outlined below for 3-bromo-4- [(2,4difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-6-[(dimethylamino)- methyl]pyridin-2(IH)-one using the aldehyde (300 mg, 0 mmol) described above and 2.0 N THF solution of dimethylamlne (500 L, i mmol) to give Ii0 mg (34%) of a colorless oil. The oil was then dissolved in MeOH (i mL) and stirred with fumaric acid (25 mg) for lh. The resulting precipitate was filtered, washed with diethyl ether, and dried to give the pure product as it's fumurate salt. IH-NMR (DMSOd 6 /400 MHz). 68.43-8.41 (m, IH) , 8.35 (s, IH) , 7.67-7.61 (m, IH) , 7.44-7.40 (m, IH) , 7.357.29 (m, 2H), 7.17-7.12 (m, IH), 6.62 (s, IH) , 6.60 (s, IH) , 5.41 (s, 2H) , 5.32 (s, 2H), 3.13 (s, 2H), 2.12 (s, 6H) . LC/MS, tr = 1.55 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 464 (M+H). Example 465 (hydroxymethyl) pyl-idin-2 (IH) -one Stepl: 4- [(2,4-difluorobenzyl)oxy]-l-(2 6-difluoropheny!)-6oxo-l,6-dihydropyridine-2-carbaldehyde. F o In a 300 ml high-pressure glass reaction vessel (16.3 g, mmol) was dissolved in 1,4-dioxane (90 mL) . The reaction vessel was sealed and immersed in a preheated oil bath at 170 C. The reaction was heated at 170° C (165 -170 °C) for 1.5 hours and then cooled to room temperature. The reaction was worked up by filtering the reaction mixture through a plug of celite and silica gel. The plug was then washed with 500 ml of methanol-CH 2 Cl 2 mixture (1:5). The filtrate was evaporated to give 14.2 g of the desired crude aldehyde. Step 2: Preparation of 4-[(2,4-difluorobenzyl)oxy]-l-(2,6difluorophenyl)-6-(hydroxymethyl)pyridin-2(iH)-one. In a 500 ml three neck round bottom flask equipped with a stir bar of 4- [(2,4-difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-6oxo-l,6-dihydropyridine-2-carbaldehyde (14.2 g, 37.7 mmol) was dissolved in methanol (200 mL). The reaction mixture was cooled to 0 °C and to this was added sodium borohydride (2.13g, 56.30 mmol) in a slow portion-wise fashion. The reaction was stirred at 0 °C for 2 hour. Excess amount of sodium borohydride was added to drive the reaction to completion. After stirring for approximately 2.5 hours, the reaction was allowed to warm to room temperature and then concentrated to dryness. The residue was taken up in ethyl acetate (i00 mL) and washed with dilute HCI (pH of aqueous layer was approximately 4). Organic extracts were washed with brine (IX ml), dried over MgSO 4 , and concentrated in vacuo. The crude product was recrystallized from ethyl acetate and hexane to yield 7.56 g (44% yield-starting from step I) of the desired alcohol. Step 3: Preparation of the title compound. In a I00 ml round bottom flask of 4-[(2,4-difluorobenzyl)oxy]- l-(2,6-difluorophenyl)-6-(hydroxymethyl)pyridin-2(iH)-one (2.49 g, 6.56 mmol), from step 2, was dissolved in acetonitrile (35 mL) . The reaction mixture was cooled to 0 °C in ice bath for i0 min. and then charged with Nbomosuccinamide (l.17g, 6.6 mmol) The mixture was allowed to stir, at 0 °C, under nitrogen atmosphere for 2 hours. The reaction was the worked up by removing the acetonitrile under vacuum. The resulting residue was then filtered, with washing from a small amount of acetonitrile, to give a yellow solid. NMR (400 MHz, DMSO-d ) 6 7.695 - 7.588 (m, 2H), 7.368-7.314 (m, 3H), 7.175 (dt, J = 8.5, 2.5, Hz, IH), 6.760 (s, IH), 5.712 (t, J = 5.674 Hz, IH) , 5.384 (s, 2H) , 4.004-3.990 (m, 2H) ; ESHRMS m/z 458.0013 (M+H-calcd for C 19 HI 3 BrF 4 NO]. requires 458.0013) . Example 466 F 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -I- (2,6-difluorophenyl) -6- (hydroxyme thyl ) pyri di n2 ( 1 H) - one The title compound was prepared by taking 4-[(2,4difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-6- (hydroxymethyl)pyridin-2(IH)-one (l.5g, 3.9 mmol) in acetonitrile (15 mL) and adding to that N-chlorosuccinimide (580 mg, 4.3 mmol). The reaction was stirred at rt for 3h afterwhich a small amount of additional N-chlorosuccinimide (50 mg, 0.4 mmol) was added to the reaction. Stirring was continued for lh. The reaction mixture was filtered through fritted funnel to obtain the crude material. IH NMR (400 MHz, 5.38 (s, 2H), 4.01 (d, J = 6.0 Hz, 2H); ES-HRMS m/z 414.0515 (M+H calcd for C 19 HI 3 CIF 4 NO 3 , requires 414.0520). Example 467 O F I F 5-bromo-4- [ (2,4-difluorobenzyl) oxy] -I- (2,6-difluorophenyl) -6-oxo-l,6-dihydropyridine-2carbaldehyde Preparation of the title compound. In a 50 ml one neck round bottom flask 4- [(2,4-difluorobenzyl)oxy]-l-(2,6difluorophenyl)-6-oxo-l,6-dihydropyridine-2-carbaldehyde (0.36 g, 0.95 mmol) was dissolved in acetonitrile (5 mL). The reaction mixture was cooled to 0 °C in ice bath and charged with N-bromosuccinamide (0.17 g, 0.95 mmol). The mixture was allowed to stir at 0 °C for 2 hours under nitrogen atmosphere After 2 hours, the solvent was evaporated under vacuum. IH NMR (400 MHz, DMSO-d 6 ) 6 9.53 (s, IH), 7.73 7.67 (m, 2H), 7.627.54 (m, IH), 7.35 (dt, J = 10.40, 2.56 Hz, IH), 7.27 (t, J=8.35 Hz, 2H), 7.19 (dt, J =8.60, 2.44 Hz, IH), 5.72 (s, IH), 5.50 (s, 2H) ; ES-MS m/z 455.9836 (M+H calcd for C gHIIBrF 4 NO requires 455.9859). Example 468 [ (dimethylamino) methyl] pyridin-2 (IH) -one In a 50 ml round bottom flask 5-bromo-4-[(2,4difluorobenzyl)oxy]-l-(2,6-difluorophenyl -6-oxo-l,6dihydropyridine-2-carbaldehyde (0.456 gm, 1.0 mmol) was stirred in dichloromethane (5 mL). To this mixture was added a 2M THF solution of dimethyl amine (1.25mi, 2.5 mmol ). The mixture was allowed to stir under nitrogen atmosphere and at room temperature for 2 hours. To this mixture was then added triacetoxy sodium borohydride (0.37 g, 1.75 mmol) followed by two to three drops of acetic acid. The mixture was then stirred at rt overnight. The solvents were then removed by evaporation and the residue was taken up in ethyl acetate (30 ml) and washed with aqueous sodium bicarbonate and brine. The organics were then combined, dried over MgS0 4 , and concentrated in vacuo. The crude product was purified by flash column chromatography using a solvent gradient of (3:1) ethyl acetate-hexane to (0:i00) ethyl acetate to give 0.14 g (30 % yield) of the desired product. IH N-MR (300 MHz, DMSO-d 6 ) 7.73-7.58 (m, 2H), 7.42-7.30 (m, 3H), 7.22 (dt, J=8.73, 2.60 Hz, IH), 6.81 (s, IH), 5.44 (s, 2H), 3.04 (s, 2H), 1.96 (s, 6H) ; ES-MS m/z 485.0 (M+H) . ES-HRMS m/z 485.0457 (M+H calcd for C 21 H sBrF 4 N20 20 requires 485.0489). Example 469 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -I- (2,6-difluorophenyl) -6- (morpholin-4 -ylmethyl) pyridin-2 (IH) -one The title compound was prepared by reacting 5-bromo-4- [(2,4-difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-6-oxo-l,6dihydropyridine-2-carbaldehyde (0.456 g, Immol) with morpholine (0.13 ml, 1.5 mmol) and triacetoxy sodium borohydride (0.42 g, 2.0 mmol) in dichloromethane (7 mL) by using a similar procedure to the one described for Example 468. The crude product was purified by flash column chromatography. Elution with (50:50 - 0:]00) hexanes-ethyl acetate to give 0.15 g (29% yield) of the desired product. IH N-MR (300 MHz, DMSO-d ) 6 7.757.57 (m, 2H), 7.43-7.31 (m, 3H), 7.20 (dt, J=8.64, 2.48 Hz, 2H), 6.85 (s, IH), 5.44 (s, 2H), 3.37 (app t, J=4.37 Hz, 4H), 3.13 (s,2H), 2.08 (t, J=4.19 Hz, 4H) ; ES-HRMS m/z 527.0600 (M+H calcd for C 2 H 20 BrF 4 N O 3 requires Example 470 F 3_br 0 m 0_ 4_[( 2, 4-diflu 0 r 0 benzyl) 0 xy]-l-(2,6-difluorophenyl)-6- { [ ( 2 -methoxyethyl ) amino] methyl } pyridin-2 (IH) -one The title compound was prepared by reacting 5-bromo-4- [( 2, 4_diflu 0 r 0 benzyl) 0 xy]-l-(2,6-difluorophenyl)-6-oxo-l,6dihydropyridine-2-carbaldehyde -(0.319 g, 0.7 mmol) with 2methoxy ethylamine (0.086 ml, 1.0 mmol) and triacetoxy sodium borohydride (0.42 g, 2.0 mmol) in dichloromethane (4 mL)by using a procedure, similar to the one described for Example 468. The crude product was purified by flash column chromatography. Elution with (50:50 0:100) hexanes-ethyl acetate to give 0.13 g of the desired product. IH NMR (400 MHz, CDCI 3 ) 6 7.54 (q, J=6.89 Hz, IH), 7.41 - 7.33 (m, IH), 7.19 (s, IH), 6.99 (t, J = 7.90 Hz, 2H), 6.90 (dt, J=7.90, 2.78, Hz, IH), 6.80 (dt, J = 10.60, 2.34 Hz, IH), 6.51 (s,IH), 5.24 (s,2H), 3.33 (t, J=4.69 Hz,IH), 3.30 (s, 3H), 2.57(t, J= 4.86 Hz, 2H) , 1.53 (s,2H) ; ES-HRMS m/z 515.0548 (M+H calcd for C 22 H 20 BrF 4 N 2 0 3 , requires 515.0594). Example 471 HoF F 5-bromo-4-[(2,4-difluorobenzyl)oxy]-i-(2,6-difluorophenyl)-6oxo-i,6-dihydropyridine-2-carboxylic acid In a 100 ml round bottom flask, 3-bromo-4- [(2,4difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-6 (hydroxymethyl)pyridin-2(iH)-one (1.70 g, 3.7 mmol) was dissolved in acetone (I0 mL) and cooled to 0 o C in ice bath. To the reaction was added IM acetone solution of Jones (5 ml, excess amount). Additional Jones reagent was added over time (approximately 6 hours) until the reaction was complete. The reaction was then concentrated down to dryness. The residue was then taken up in ethyl acetate (i0 mL) and washed with brine. The dark yellow to brown colored crude product was purified by dissolving in IN aqueous NaOH. The remaining organic impurities were removed by extracting with diethyl ether. The organic layers were discarded and the aqueous layer was acidified with dilute HCI (til pH app I) to precipitate the pure acid which was then filtered and triturated with ether to obtain 1.17 g (65%) of the desired product. IH NMR (400 MHz, DMSO-d 6 ) 6 7.66 (q, J= 9.41 Hz, IH), 7.577.50 (m, IH), 7.34 (dt, J= i0.ii, 2.78 Hz, IH), 7.287.23 (m, 3H), 7.18 (dt, 8.90, 2.42 Hz, IH), 5.47 (s, 2H) . ES- HRMS m/z 471.9814 (M+H calcd for C 19 HIIBrF 4 NO 4 , requires Example 472 COOCH 3 Methyl 4- [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl] -3-methylbenzoate Step: Preparation of methyl 4-(4-hydroxy-6-methyl-2oxopyridin-l(2H)-yl)-3-methylbenzoate OH COOCH 3 In a 50 ml one neck round bottom flask equipped with a stir bar, Dean Stark trap, and condenser 4-amino-2-methylmethylbenzoate (l.19g, I1.63 mmol) and 4-hydroxy-6-methyl-2Hpyran-2-one (l.611g, 12.78 mmol) were mixed together and dissolved in 1,2-dichlorobenzene (5 mL). The mixture was vigorously stirred and then placed in a preheated oil bath at 165 0 °C. The reaction was maintained at 165 0 °C for 1.5 hour and cooled to room temperature. The reaction was worked up by diluting with toluene (i0 mL) and then stirring at room temperature for 2 hours. A light brown precipitate resulted. The crude product was isolated by filtration and then triturated with ether. H NMR (400 MHz, DMSO-d 6 ) 6 10.64 (s, IH), 7.93 (s,iH), 7.85 (dd, 8.46 Hz, 1H), 7.26 (d , J= 8.12 Hz, IH) , 5.91 (d, J= 2.32 Hz, !H), 5.54 (d, J=2.32 Hz, IH), 3.84 (s, 3H), 1.99 (s, 3H), 1.73 (s,3H) . ES-HRMS m/z 272.0880 (M-H ca!cd for C sHI 4 N0 4 . requires 272.1001) . Step 3: Preparation of Methyl 4-(3-bromo-4-hydroxy-6methyl-2-oxopyridin-i (2H)-yl)-3-methylbenzoate OH COOCH 3 Methyl 4-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-l(2H)- yl)-3-methylbenzoate was prepared by reacting - methyl 4-(4hydroxy-6-methyl-2~oxopyridin-l(2H)-yl)-3-methylbenzoate with N-bomosuccinamide in acetonitrile by following a procedure, similar to the one described in Example 465step 3. IH NMR (400 MHz, DMSO-d 6 ) 6 7.95 (s, IH), 7.87 (dd, J = 7.76, 2.02 Hz, IH), 7.31 (d, J=8.54, IH), 6.09 (s,IH), 3.85 (s, 3H), 1.99 (s,3H), 1.74 (s, IH) . ES-HRMS m/z 352.0195 (M+H calcd for CIsHI 4 BrNO 4, requires 352.0185) Step 4: The title compound was prepared by taking methyl 4- (3-bromo-4-hydroxy-6-methyl-2-oxopyridin-l(2H)-yl)-3methylbenzoate (0.92 g, 2.61 mmol) and dissolving in dry DMF (5 mL) . Potassium carbonate (0.432 g, 3.13 mmol) and 2,4 Difluuorobenzyl bromide (0.335 ml, 2.61 mmol) were then added. The mixture was allowed to stir at room temperature for 2 The reaction was then worked up by pouring it into i00 ml of ice-water which resulted in a precipitate forming which was isolated by filtering through a fritted funnel. The crude product was washed with ether and dried in vacuum to give 0.85 g (76.20%) of pure product. IH NMR (400 MHz, DMSO-d 6 ) 6 7.98 (d, J = 1.6 Hz, IH) , 7.88 (dd, J =8.04, 2.0 Hz, IH) , 7.69 (q, J = 8.6 Hz, IH), 7.36-7.30 (m, 2H), 7.17 (dr, J = 8.7, 2.3 Hz, IH), 6.71 (s,IH), 5.32 (s,2H), 3.86 (s,3H), 2.00 (s,3H), 1.86 (s, 3H) . ES-HRMS m/z 478.0459 (M+H calcd for C 22 HIgBrF 2 NO 4 requires 478.0466) . Examples 473-476 The compounds of Examples 473-476 are prepared by derivitazion of the compounds of Example 472. Compound No. R Ex. 473 - CO 2 H Ex. 474 - CH 2 OH Ex. 475 C (O) NH (CH 2 ) 2 OCH 3 Ex. 476 c (o) NHCH 3 M+H ESHRMS MF Requires m/z C 21 HI 6 BrF 2 NO 4 464.0310 464.0324 C 21 HIsBrF 2 NO 3 450.0500 450.0517 C 24 HnBrF N 2 0 4 521.0888 521.0865 C 22 H 20 BrF 2 N 2 0 3 477.0626 477.0609 NMR characterization of compounds of Examples Ex. No. NMR Data 473 H-NMR [400 MHz, D,MSO-d ) 6 13,11 (s, IH) 7.95 IH), 7.86 (dd, J=7.88, 1.91 Hz, IH), 7.67 (dq, IH) 0 7.36-7.30 (m, 2H), 7.17 [dt, J =8.54, 2.48 (s,IH), 5.32 (s,2H), 1.99 (s, 3H), 1.87 (s, 3H) 474 H NMR (400 MHz, DMSO-d ) 6 7.67 (q, J =8.5 Hz, =10.04, 2.77 Hz, IH), 7.32 (s, IH), 7.24 (dd, IH) , 7.17 (dt, J = 8.84,2.6 Hz, IH) , 7.08(d, 6.66 (s,IH), 5.30 (s, 2H), 5.25 (t, J = 6.01 =6.68 Hz, 2H) , 1.91 (s, 3H ), 1.86 (s,3H) 475 H NMR (400 MHz, DMSO-d 6 ) 6 8.58 (app t, J =5.4 (s,IH), 7.76 (dd, J= 8.05, 1.63 Hz, IH), 7.68 Hz, IH) j 7.33 (dr, J=9.76, 2.03 Hz, IH), 7.27 7.17 (ddt, J=8.51, 2.63, 0.91 Hz, IH), 6.70 (s, 4.50 (t, J=5.6 Hz , IH) , 3.47-3.36 (m, 4H) , (s,3H) , 1.87 (s,3H) 476 IH NMR {400 MHz, DMSO-d ) 6 8.50-8.49 (m, IH), (dd, J=8.22, 1.79 Hz, IH), 7.69 (q, J= 6.75 Hz, 9.88, 2.57 Hz, IH), 7.26(d, J=8.52 Hz, IH), 7.17(dr, Hz, IH), 6.69 (s, IH), 5.31 (s, 2H), 2.77 (d, 1.93 (s, 3H) , 1.86 (s, 3H) Example 477 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methylI- vinylphenyl ) pyridin-2 (IH) -one Step iPreparation of -l-(4-bromo-2-methylphenyl)-4hydroxy-6-methylpyridin-2(IH)-one The title compound was prepared in a similar manner to the procedure outlined above for 4-(4-hydroxy-6-methyl-2oxopyridin-I (2H)-yI)-3-methylbenzoate. IH NMR (400 MHz, DMSOd 6) 6 I0.61 (s, IH) , 7.59 (d, J= 2.84 Hz, IH) , 7.45 (dd, J= 8.39, 2.44 Hz, IH), 7.06 (d, J= 7.44, iH) , 5.89 (d, J=2.73 Hz, IH), 5°53(d, J=2.30, IH), 1.91 (s, 3H), 1.75 (s, 3H) . ESHRMS m/z 294.0127 (M+H calcd for C 13 HI 3 BrNO 3 . requires 294.0130). Step 2- ?reparation of - l-(4-bromo-2-methylphenyl)-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one F 8r l-(4-bromo-2-methylphenyl)-4-hydroxy-6-methylpyridin-2 (IH)-one (7.35 g, 25.0 mmol) was dissolved in DMF (15 mL) and stirred with potassium carbonate (4.14 g, 30.0 mmol) and 2,4 difluorobenzyl bromide (3.21 ml (25.0 mmol) at room temperature for 2 hours. The reaction was worked up by pouring in to 300 ml ice water under continuous stirring. A white precipitate was obtained which was isolated by filtering and further purified by triturating with ether to give 3.06 g (29%) of the desired product. H NMR (400 MHz, DMSO-d 6 ) 6 7.657.59 (m, 2H) , 7.49 (dd, J=8.45, 2.22 Hz, IH) , 7.31 (dt, J= 9.79, 2.22 Hz, IH), 7.167.08 (m, 2H), 6.05 (d, J= 2.58 Hz, IH) 5.93 (d, J= 2.66 Hz, IH) , 5.08 (s, 2H) , 1.93 (s, 3H) , 1.77 (s, 3H). ES-HRMS m/z 420.0390 (M+H calcd for C; 0 HI BrF 2 N0 requires 420. 0411) . Step 3: Preparation of 4-[(2,4-difluorobenzyl)oxy]-6-methyll-(2-methyl-4-vinylphenyl)pyridin-2(IH)-one. F In a 50 ml round bottom flask previously evacuated and filled with nitrogen, l-(4-bromo-2-methylphenyl)-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2 (IH)-one (0.420 g, 1.0 mmol) was dissolved in dry THF (i0 mL). To this mixture was added Pd (PPh 3 ) 4 (0.173 g, 0.15 mmol). The reaction flask was sealed with a rubber septum, evacuated and filled with nitrogen. Under a nitrogen atmosphere, tributyl(vinyl)tin (0.35 ml, 1.2 mmol) was added to the sealed reaction mixture and stirred overnight at 50 °C. The reaction was worked up by quenching with water and extraction of the product with ethyl acetate. The crude product was purified by column chromatography. Elution with ethyl acetate-hexanes (50:50 - 0:100) gave 0.32 g (69%) of the desired product. Step 4: The title compound was prepared by reacting 4- [ (2,4-difluorobenzyl) oxy] -6-methylI- (2-methyl-4vinylphenyl)pyridin-2(iH)-one (0.64 9, 1.74 mmol) with Nbromosuccinamide {0.325 g, 1.83 mmol) in acetonitrile (9 mL) at 0°C using a similar procedure as described in step 3 of Example 465, to give 0.423 g (54.5 % after recrystallization) of the desired product, iH NMR (400 MHz, DMSO-dG) 5 7.67(app q, J= 7.59 Hz, IH) , 7.48(s,IH), 7.42(dd, J=8.21,i.98 Hz,IH), 7.33(dt, J=10.00, 2.27 Hz, IH), 7.17(tit, J=8.51, 2.44 Hz, IH), 7.13(d, J=7.88 Hz, IH) 6.74(dd, J=ii.29, 6.34 Hz, IH), 6.67 (s,IH), 5.88(d, J= 17.85, IH), 5.32-5.30 (m, 2H), 1.92 (s, 3H), 1.88 (s,3H) . ES-HRMS m/z 446.0579 (M+H calcd for C 22 HIgBrF 2 NO 2, requires 446.0568) . Example 478 F OH 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-[4-(l,2-dihydroxyethyl)- 2-methylphenyl]-6-methylpyridin-2(iH)-one 3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-l- (2-methyl4-vinylphenyl)pyridin-2(IH)-one (0.126 g, 0.28 retool) was dissolved in a mixture of acetone (3 mL) and water (i mL). To this was added 4-methy!morpholine N-oxide (0.032 g, 0.28 mmol) and catalytic amount (approximately 5 mgs) of osmium tetroxide was added, and stirred under nitrogen atmosphere. After approximately 2 hours, the reaction was worked up by evaporation of the acetone. The product was extracted into ethyl acetate and concentrated to give a dark colored solid which was further purified by column chromatography to give 0.049 g (37 % yield) of charcoal colored solid. H NMR (400 MHz, DMSO-d 6 ) 6 7.67 (q, J=8.24 Hz, IH), 7.37-7.23 (m, 3H), 7.17 (dr, J= 8.62, 2.62 Hz, IH), 7.07 (dd, J=9.36, 2.24 Hz, IH), 6.65(s,iH), 5.30 (s, 2H) , 4.74(t, J=6.16Hz, IH) , 4.574.50 (m, IH), 3.45(app t, J=6.12 Hz, 2H), 3.413.37 (m, IH) , I. 91 (s, 3H) , 1.85 (s, 3H) . ES-HRMS m/z 480. 0625 (M+H calcd for C 22 H 21 BrF 2 NO 4. requires 480.0623) . Example 479 H 3 COOC Cj methyl 3- [3-bromo-4- [(2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl] -4-chlorobenzoate Step I: Preparation of methyl 4-chloro-3-(4-hydroxy-6methyl-2-oxopyridin-l(2H)-yl)benzoate. A condensation reaction with methyl 3-amino-4-chlorobenzoate (14.5g, 78.2 mmol) and 4-hydroxy-6-methyl pyranone under reaction condition similar to the one described in Example 465step 3 gave 12.32 (53.8%) of desired product. Step-3Preparation of methyl-4-chloro-3-[4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]benzoate. F H 3 COOC In a 250mi round bottom flask, methyl 4-chloro-3-(4hydroxy-6-methyl-2-oxopyridin-l(2H)-yl)benzoate (5.28 g, 18.0 mmol) from stepl was reacted with 2,4-difluoro-benzylbromide (3.72 g, 18.0 mmol) in DMF using similar procedure as in Example 472 step 3. After aqueous work up and chromatographic purification, 2.3 g (30%) pure product was obtained. Step 4: methyl 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]-4-chlorobenzoate was prepared by reacting methyl-4-chloro-3-[4- [(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]benzoate (2.3 g, 5.47 mmol) with N-bromosuccinamide (0.97 g, 5.47 mmol) in acetonitri!e (!0 mL) at 0°C, using a similar procedure as described in step 3 of Example 465, to give 1.80g (66.2 %) of the desired product. IH NMR (400 MHz, DMSO-d 6 ) 6 8.06-8.03 (m, 2H), 7.86 (d, J=9.70 Hz, IH), 7.68 (q, J= 7.62, IH), 7.34(dt, J=10.07, 2.46 Hz, IH), 7.17 (dt,J= 8.72, 2.90 Hz, IH), 6.73 (s,lH), 5.33 (s, 2H), 3.85 (s, 3H) , 1.91 (s, 3H) . ES-MS m/z 495.9757 (M-H calcd for C 21 HI 4 BrCIF 2 NO 4 . requires 495.9795) . Example 480 HOOC 3- [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-4-chlorobenzoic acid In a 50 ml round bottom flask, methyl-4-chloro-3-[4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]benzoate (0.450 g, 0.90 mmol) was stirred in THF (5 mL]. To this mixture was added NaOH (0.120 g, 3.0 mmol ) as a solution in water (1.5 mL) . The reaction mixture was stirred at room temperature overnight. The THF was evaporated and the residue was acidified with dilute HCI. A white precipitate was obtained. The product was filtered, washed with water and dried in vacuum to give 0.375 g (86 % yield ) of the desired product. IH NMR (400 MHz, DMSO-d 6 ) 6 7.89 (dd, J=7.78, 1.73 IH), 5.32(s, 2H), 1.89 (s,3H). ES-MS m/z 481.9585 (M-H calcd for C 20 HI 2 BrCIF 2 NO 40 requires 481.9601) . Example 481 O 3-bromo-4- [ (2,4-difluorobenzyl)oxy] -!- [5- (hydroxymethyl) -2methylphenyl ] -6-methylpyridin-2 (IH) -one Step i: Preparation of 4-hydroxy-l- [5-(hydroxymethyl)-2methylphenyl]-6-methyl pyridine-2(iH)-one HO O 4-Hydroxy-6-methyl-2-pyrone (23.0 g, 182.2 mmol) and 3-Amino4-methylbenzyl alcohol (25.0 g, 182.2 mmol) were taken up in ml of 1,2-dichlorobenzene. The solution was heated to 165°C in a 250 ml round bottom flask equipped with a J-Kem temperature controller probe, and a heating mantle. In a separate 250 ml round bottom flask 4-Hydroxy-6-methyl-2-pyrone (23.0 g, 182.2 mmol) was suspended in 25 ml of 1,2dichlorobenzene and also heated to 165°C. The pyrone solution was poured into the flask containing the aniline and the reaction stirred at 165°C for 20 minutes. The reaction was allowed to cool to room temperature. Reaction contents were washed with saturated NaHCO 3 (aq.). Separated the organic and aqueous layers. Aqueous layer was made acidic with dropwise addition of concentrated HCl. The product was extracted from the acidic aqueous layer with n-BuOH. N-BuOH removed in vacuo to produce a reddish brown oil. (8°5 g, 19%). Contents carried forward to next reaction with no further purification. IH NMR (300 MHz, CD 3 OD) 6 7.35 (m, 2H), 7.08 (s, IH), 6.08 (br s, IH), 5.81 (br s, IH), 4.60 (s, 2H], 2.01 (s, 3H), 1.87 (s, 3H) . LC/MS, tr = 1.42 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 246.1131 (M+H) . ES-HRMS m/z 246.1107 (M+H calcd for C 14 HI 6 NO 3 requires 246.1125) . Step 2: 4-[(2,4-difluorobenzyl)oxy]-l-[5-(hydroxymethyl)-2methylphenyl]-6-methyl-pyridin-2(IH)-one O OH 4-hydroxy-l-[5-(hydroxymethyl)-2-methylphenyl]-6-methyl pyridin-2(IH)-one ( from Step I) 8.0 g, 32.6 mmol) was stirred briskly at room temperature with 2,4-difluorobenzyl bromide (4.2 ml, 32.6 mmol) and K 2 C0 3 (4.5 g, 32.6 mmol) in ml of dimethylformamide. After stirring for 8 hours, H 2 0 (I00 ml) was added to reaction mixture. The product was extracted with ethyl acetate. Ethyl acetate layer was separated and dried over Na 2 SO 4 . Ethyl acetate was removed in vacuo. A yellow oil was obtained. silica gel first eluting The oil was passed through a plug of with 500 ml of ethyl acetate/hexane (I:I). This eluent was set aside. Next, ethyl acetate (100%) was passed through the plug until desired product was completely flushed from silica (3 liters) . Solvent was removed in vacuo. Light yellow oil obtained (7.5 g, 62%). IH NMR (300 MHz, CODED) 6 7.60 (app q, J = 6.44 Hz, IH), 7.42 (d, J = .81 Hz, 2H) , 7.15 (s, IH), 7.06 (m, 2H) , 6.21 (dd, J = 1.61, 1.00 Hz, IH), 6.12 (d, J = 2.62 Hz, ill), 5.16 (s, 2H), 4.65 (s, 2H) , 2.07 (s, 3H) , 1.93 (s, 3H) ; LC/MS, tr = 2.38 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 372 (M+H) . Step 3 : Preparation of the title compound 4- [ (2,4difluorobenzyl) oxy] - i- [5- (hydroxymethyl) -2-methylphenyl ] -6methyl-pyridin-2(IH)-one ( from Step 2) (4.0 g, 10.8 retool) was stirred at room temperature with N-bromosuccinimide (2.1 g, 11.9 mmol) in i00 ml of CH 2 C1 2 for 2.0 hours. The reaction was evaporated on a rotary evaporator and the resulting solid was washed with acetonitrile and dried in vacuo to yield a white solid (3.9 g, 80%). IH NMR (300 MHz, CDCI 3 ) 6 7.67 (app q, J = 6.24 Hz, IH) , 7.35 (d, J = 1.01 Hz, 2H) , 7.10 (s, IH) , 7.04 (m, IH) , 6.91 (ddd, J = 11.08, 8.66, 2.42 Hz, IH), 6.15 (d, J = 0.63 Hz, 2H) , 5.29 (s, 2H) , 4.66 (s, 2H) , 2.08 (s, 3H) , 1.97 (s, 3H) ; ES-MS m/z 450 (M+H). ES-HRMS m/z 450.0467 (M+H calcd for C 21 HIgBrF 2 NO 3 requires 450.0511). Example 482 3-chloro-4-[(2,4-difluorobenzyl)oxy]-l-[5-(hydroxymethyl -2methylpheny!]-6-methylpyridin-2(iH)-one The title compound was prepared by a procedure similar to the one described for Example 481, except that the product from Step 2, Example 481 was chlorinated instead of being brominated. The procedure is as follows: 4-[(2,4difluorobenzyl)oxy]-l- [5- (hydroxymethyl)-2-methylphenyl]-6methyl-pyridin-2(iH)-one (from Step 2, Example 481 above) (7.0 g, 18.8 mmol) was refluxed with N-chlorosuccinimide (2.5 g, 18.8 mmol) in 50 ml of CH 2 C1 2 overnight. The reaction was evaporated on a rotary evaporator and the resulting solid was stirred in MeOH. The precipitate was collected on a filter pad, washed with MeOH and dried in vacuo to yield a white solid (1.6 g, 21%). IH NMR (300 MHz, DMF-d ) 6 7.85 (app q, J = 6.44 Hz, IH), 7.43 (d, J = 0.81, IH), 7.42 - 7.23 (m, 3H) , 6.84 (s, IH), 5.48 (s, 2H), 4.67 (s, 2H) , 2.05 (s, 3H), 2.03 (s, 3H) ; ES-MS m/z 406 (M+H) . ES-HRMS m/z 406.1033 (M+H calcd for C 2 HI CIF 2 NO 4 requires 406.1016). Example 483 Cl O 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-[5-(hydroxymethyl)-2methylphenyl]-6-methylpyridin-2(IH)-one Step I: Preparation of 3-amino-4-chloro-benzyl alcohol 3-Nitro-4-chloro-benzyl alcohol (23.0 g, 122.6 mmo!) is taken up in isopropyl alcohol (175 ml) and water (35 ml) . Iron powder (<I0 micron) (68.0 g, 1.2 moles) and NH 4 CI (66.0 g, 1.2 moles) are added. The suspension is stirred overhead at 70°C in a three neck round bottom flask equipped with a heating mantle and a J-Kem temperature controller probe. After 4 hours, isopropyl alcohol was removed in vacuo. Water (i00 ml) and concentrated HCI (i0 ml) was added to mixture. Contents are transferred to a separtory funnel and ethyl acetate is used to extract the aqueous layer of impurities. The aqueous layer was then basified with 50% aqueous NaOH. The product was extracted from the basic aqueous layer with ethyl acetate. The ethyl acetate layer was dried over Na 2 S0 4 and then removed in vacuo. The remaining residue was taken up in 50% ethyl acetate/hexane and the precipitate was collected on a filter pad. Precipitate was washed with 50% ethyl acetate/hexane to yield a flocculent brown solid (8.4 g 0 44%). IH NMR (300 MHz, CODED) 6 7.17 (d, J = 8.26 Hz, IH), 6.86 (d, J = 2.01 Hz, IH) , 6.66 (dd, J = 2.01, 0.61 Hz, IH), 4.51 (s, 2H) ; LC/MS, tr = 0.32 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254" nm, at 50°C) ; ES-MS m/z 158 (M+H) . Step 2: l-[2-chloro-5-(hydroxymethyl)phenyl]-4-hydroxy-6methylpyridin-2(IH)-one 3-amino-4-chloro-benzyl alcohol (8.0g, 51.0 mmol) and 4hydroxy-6-methyl-2-pyrone (6.4 g, 51.0mmol) were taken up in 1,2-dichlorobenzene (50 ml) . The mixture was plunged into a 165°C oii bath where it stirred for 20 minutes. The reaction was cooled to room temperature and the reaction was worked up by washing with saturated NaHCO (aq.) and extracting impurities with ethyl acetate. The product remained in the aqueous layer. The basic aqueous layer was made acidic with concentrated HCI. The product was extracted from the acidic aqueous layer with ethyl acetate. The ethyl acetate layer was dried over Na 2 S0 4 and the solvent removed in vacuo. The product was obtained as a yellow oil in a 26% yield and was carried through to the next step with no further purification. IH NMR (300 MHz, CD 3 OD) 6 7.62 (d, J = 8.26 Hz, 2H), 7.51 (dd, J = 8.46, 2.22 Hz, 1H), 7.36 (d, J = 2.01 Hz, IH), 6.13 (br s, IH) , 5.84 (d, J = 2.42 Hz, IH) , 4.68 (s, 2H), 1.97 (s, 3H) ; LC/MS, tr = 0.25 minutes and 1.41 minutes (tautomer), 5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 266 (M+H). Step 3 : l-[2-chloro-5-(hydroxymethyl)phenyl]-4- [ 2,4di f luorobenzyl ) oxy] - 6 - me t hylpyridin2 ( IH ) - one c, 1 - [ 2 - chl oro - 5 - ( hydroxyme thy! ) phenyl ] - 4 - hydroxy6 - methylpyridin-2(1H)-one ( from step 2) (3.5g, 13.2 mmol was taken up in DMF (10 ml) and cooled to 0°C. 2,4-Difluorobenzyl bromide (1.7 ml, 13.2 retool) and K 2 C0 3 (1.8 g, 13.2 mmol) were added and the reaction stirred for 6 hours. The reaction was worked up by adding saturated NaHCO 3 (aq.) and extracting with ethyl acetate. The ethy! acetate extraction was washed with water, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over Na 2 SO 4 , filtered, and the solvent removed in vacuo. The product was obtained in 83% crude yield and carried through to the next step as a brown oil. LC/MS, t= = 2.48 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) • ES-MS m/z 392 (M+H) . ES-HRMS m/z 392.0853 (M+H calcd for C 20 HITCIF 2 NO 3 requires 392.0860). Step 4: The title compound was prepared from l-[2-chloro-5- (hydroxymethyl)phenyl]-4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(IH)-one (from step 3) (l.8g, 4.6 mmol) and N- bromosuccinimide (0.82 g, 4.6 mmol) by dissolving them in CH 2 C1 2 (I0 ml) and stirring for 2 hours at room temperature. The solvent was removed in vacuo and the residue was taken up in CHHCN. The precipitate was collected on a filter pad and rinsed with CH 3 CN to yield a white solid (370 mg, 17%). H NMR (300 MHz, CDCI 3 ) 6 7.65 (app q, J = 6.24 Hz, IH), 7.52 (d, j = 8.26 Hz, IH), 7.40 (dd, J = 8.26, 2.01 Hz IH), 7.26 (d, J = 0.81 Hz, IH) 0 7.03 (m, IH), 6.91 (ddd, J = 11.08, 8.66, 2.42 Hz, IH), 6.17 (d, J = 0.81 IH) , 5.29 (s, 2H) , 4.63 (s, 2H) , 2.02 (s, 3H) ; ES-MS m/z 471 (M+H) . ES-HRMS m/z 471.9953 (M+H calcd for C 20 HI 6 BrCIF 2 NO 3 requires 471.9944). Example 484 methylphenyl]-6-methylpyridin-2(iH)-one The title compound was prepared from l-[2-chloro-5- (hydroxymethyl)phenyl]-4-[(2,4-difluorobenzyl)oxy]-6methv!pyridin-2(iH)-one (2.4 g, 6.1 mmol) and NCS (815.0 mg, 6.1 mmol) in 65°C dichloroethane (20 ml) . A catalytic amount of dichloroacetic acid (2 drops) was added. After two hours the solvent was removed in vacuo and the residue was taken up in diethyl ether. The precipitate was collected on a filter pad and then taken up in 50% ethyl acetate/hexanes to remove residual succinimide. The precipitate was collected on a filter pad and then dried in vacuo to produce a white powder (180 mg, 6.9%). IH NMR (300 MHz, CDCI 3 ) 6 7.61 app q, J = 6.44 Hz, IH), 7.52 (d, J = 8.26 Hz, IH), 7.40 (dd, J = 8.26, 2.01 Hz IH), 7.27 (d, J = 2.01 Hz, IH) , 7.00 (m, IH), 6.91 (m, IH), 6.20(s, IH), 5.29 (s, 2H), 4.65 (s, 2H) 2.03 (s, 3H) ; ES-MS m/z 426 (M+H) . ES-HRMS m/z 426.0453 (M+H calcd for C 0 HI 6 CI2F NO requires 426.0470) . Example 485 O I HCI 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-{5- [(dimethylamino)methyl]-2-methylphenyl}-6-methylpyridin-2(IH)- one hydrochloride Step i: Preparation of 3-[3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4methylbenzaldehyde O 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-[5-(hydroxymethyl)-2methylphenyl]-6-methylpyridin-2(IH)-one (l. Sg, 3.33 mmol) was dissolved in 75% CH 3 CN/CH 2 CI 2 (20ml) and cooled to 0°C. DessMartin periodinane(2.8 g, 6.66 mmol) was added and the reaction stirred for four hours. At this time, the reaction was quenched with 5% sodium bisulfite (aq.) . The product was extracted with ethyl acetate. The combined organic extracts were then washed with saturated NaHCO (aq.). The aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over Na 2 SO 4 , filtered, and concentrated. The resulting residue was taken up in diethyl ether and the precipitate was collected on a filter pad and washed with more diethyl ether to yield a white solid (1.35 g, 91%). IH NMR (300 MHz, CDCI 3 ) 6 10.00 (s, IH), 7.91 (dd, J = 7.65, 1.61 Hz, IH), 7.65 (m, 2H), 7.57 (d, J = 7.85 Hz, IH), 7.03 (m, IH), 6.95 (ddd, J = 12.69, 8.86, 2.62 Hz, 1H), 6.19 (s, IH), 5.31 (s, 2H), 2.20 (s, 3H), 1.96 (s, 3H) ; ES-MS m/z 448 (M+H) . ESHRMS m/z 448.0347 (M+H calcd for C 21 HITBrF 2 N0 3 requires 448.0354). Step 2: Preparation of the title compound 3-[3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4methylbenzaldehyde ( from step I) (0.50 g, i.Ii mmol) was dissolved in CH 2 C1 2 ( I0 ml). N,N-dimethylamine (2.0 M in THF) (I.Ii ml, 2.22 mmol) was added. This mixture stirred for at room temperature for 12 hours. Next, sodium tri - acetoxyborohydride (0.47 g, 2.22 mmol) was added and the reaction stirred for two more hours. The reaction was washed with 1 N NaOH (aq.) and then extracted with CH C! 2 . The combined organic extracts were washed with water. The aqueous layer was separated and extracted with CH 2 C1 2 . The combined organic extracts were dried over Na 2 SO filtered and concentrated in vacuo. The resulting residue was taken up in diethyl ether. IM HCI in diethyl ether (5 ml) was added and the precipitate was collected on a filter pad. This precipitate was hygroscopic. The hygroscopic solid was then taken up in hot ethy! acetate. Hexane was added until a precipitate crashed out. The precipitate was collected on a filter pad to yield a white solid (150 rag, 26%) . IH NMR (400 MHz, D 2 0) 6 7.42 (m, 3H), 7.17 (S,IH), 6.86 (m, 2H) , 6.53(s, IH), 5.20(S, 2H), 4.18(s, IH), 2.72(s, 6H), 1.85 (s, 3H) , 1.82(s, 3H) ; ES-MS m/z 477 (M+H). ES-HRMS m/z 477.0955 (M+H calcd for C 23 H 24 BrF 2 N 2 02 requires 477. 0984) . O Example 486 HC1 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-{5- [(isopropylamino)methyl]-2-methylphenyl}-6-methylpyridin2(iH)-one hydrochloride The title compound was prepared by reductive amination of 3- [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin_ l(2H)-yl]-4-methylbenzaldehyde ( from step I) (0.50 g, I.ii mmol) with iso-propyl amine (0.13 g, 2.22) according to the procedure described above for Example 485 (Step 2) to give the desired compound (0.49g, 84%). IH h%4R (400 MHz, CD 3 OD) 6 7.64 (app quartet, J = 6.58 Hz, IH), 7.53 (m, 2H), 7.29(br s, IH) , 7.03(m, IH) , 6.68 (s, IH) , 5.36 (s, 2H), 4.22(s, 2H), 3.46(m, IH), 2.06 (s, 3H), 2.01 (s, 3H), 1.37 (d, J = 6.58 Hz, 6H) ; ES-MS m/z 491 (M+H) . ES-HRMS m/z 491. 1107 (M+H calcd for C_ 04 H 26 BrF 2 N 2 02 requires 491.1140). Example 487 F O N OH H 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-meth¥1-2-oxopyridinl(2H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide HO O O OCH 3 Step 1 : Preparation of methyl 3 - (4hydroxy-6-methyl-2oxopyridin1 (2H) -yl ) - 4 -me thylbenzoate 4-Hydroxy-6-methyl-2-pyrone (22.9 g, 181.6 mmol) and methyl-3-amino-2-methylbenzoate (25 g, 151.3 mmol) were suspended in 50 ml of 1,2-dichlorobenzene in a 250 ml, 3necked round bottom flask equipped with a J-Kem temperature controller probe, a Dean-Stark trap, and a heating mantle. The reaction was heated to !65°C for 15 minutes, during which, water and some 1,2-dichlorobenzene was collected in the DeanStark trap. The reaction was allowed to cool to about II0eC. At this point, 200 ml of toluene was added. The flask was plunged into a 0°C ice bath while stirring. "Oiling out" occurred. Perhaps too much toluene was added so some of the solvent was removed in vacuo. The oil went back into solution and a light brown precipitate remained. The toluene mixture was allowed to stir for 72 hours at room temperature. A precipitate was collected on a filter pad. The precipitate was filtered and washed 3 times with toluene, 3 times with 50°C. water to remove excess pyrone, and dried in vacuo to give a tan solid (16.5 g, 40% yield). IH NMR (300 MHz, CD 3 OD) 6 8.06 (dd, J = 8.06, 1.61 Hz, IH), 7.80 (d, J = 1.61 Hz, IH), 7.56 (d, J = 8.06, Hz, IH), 6.15 (dd, J = 2.42, 0.81 Hz, IH), 5.86 (d, J = 2.42 IH) , 3.94 (s, 3H) , 2.15 (s, 3H), 1.91 (s, 3H) ; ES-MS m/z 274 (M+H) . ES-HRMS m/z 274.1066 (M+H calcd for C 1 sH 16 NO requires 274.1074). Step 2: Preparation of methyl 3-[4-[(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]-4-methylbenzoate Methyl 3-(4-hydroxy-6-methyl-2-oxopyridin-l(2H)-yl)-4methylbenzoate ( from Step I) (16.5 g, 60.4 mmol) 2,4difluorobenzyl bromide (7.8 ml, 60.4 mmol) were taken up in 250 ml of N,N-dimethylformamide and the mixture was cooled to 0°C. K 2 C0 3 (8.3g, 60.4 mmol) was added and reaction stirred for 12 hours during which time the reaction was allowed to warm to room temperature. LC/MS indicated the presence of starting material after 12 hours. An excess of K 2 C0 3 was added at room temperature along with 0.50 ml of 2,4-difluorobenzyl bromide. The reaction stirred for an additional two hours. Saturated NaHCO 3 (aq.) was poured into reaction vessel. The solution was extracted with ethyl acetate and the organic layers were combined then washed with water. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over Na 2 SO 4 , and evaporated. The product was carried on to the next step as a crude oil (24.1 g, quantitative yield). H NMR (300 MHz, CDCI]) 6 8.06 (dd, J = 7.85, 1.61 Hz, IH), 7.82 (d, J = 1.61, IH) , 7.52-7.44 (m, 2H), 7.01 - 6.88 (m, 2H), 6.05 (d, J = 2.62 Hz, IH), 5.97 (dd, J = 2.62, 0.81 Hz, IH), 5.08 (s, 2H) , 3.93 (s, 3H) , 2.20 (s, 3H) , 1.89 (s, 3H) ; ES-MS m/z 400 (M+H) . ES-HRMS m/z 400.1374 (M+H calcd for C 22 H 20 F 2 N0 4 requires 400.1355) . Step 3: Preparation of 3-[4-[(2,4-difluorobenzyl)oxy]-6- methyl-2-oxopyridin-l(2H)-yl]-4-methylbenzoic acid o OH Methyl 3-[4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-4-methylbenzoate (14g, 35.0 mmol) (from step 2) was taken up in THF (25 ml) and H 2 0. 2.5 N NaOH (aq.) was added and the reaction stirred for 30 minutes at room temperature. The reaction was made acidic via the addition of concentrated HCI. The product was extracted with ethyl acetate. The ethyl acetate extraction was dried over Na 2 S0 4 , filtered, and the solvent removed in vacuo. Upon vacuum removal of the solvent, the product crashed out of the ethyl acetate. This precipitate was collected on a filter pad and washed with a 50 ethyl acetate/hexanes to yield a white powder (9g, 7%). IH NMR (300 MHz, CDCI 3 ) 8.01 (dd, J = 1.61 Hz, IH), 7.84 (d, J = 1.61 Hz, IH), 7.52 - 7.47 (app q, J = 8.26, IH), 7.43 (d, J = 8.06 Hz, IH) , 7.00 - 6.88 (m, 2H) 6.19 (d, J = 2.62 Hz, IH), 6.05 (dd, J = 2.62, 1.81 Hz, IH) 5.17 (s, 2H) , 2.19 (s, 3H) , 1.90 (s, 3H) ; ES-HR/MS m/z 386.12 (M+H calcd for C 2 zH sF 2 N0 4 requires 386.1198). Step 4: Preparation of 3- [3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4methylbenzoic acid F\ O OH 3- [4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridinl(2H)-yl]-4-methylbenzoic acid (5.9 g, 15.2 mmol) (from step 3 above) was taken up in dichloromethane (25 ml) . NBromosuccinimide was added and the reaction stirred for 14 hours. The dichloromethane was removed in vacuo and the residue was taken up in acetonitrile. The precipitate was collected on a filter pad and rinsed with acetonitrile to yield the desired product as a white solid (5.2 g, 74%). H (M+H) . ES-HRMS m/z 464.0275 M+H calcd for C IHI BrF 2 N0 requires 464.0304). Step 5: Preparation of the title compound. 3-[3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-20 x 0 pyridin_ 1 ( 2 H)_y 1 ]_ 4 _ methylbenzoic acid (from Step 4 above) (l.9g, 4.10 mmol) was dissolved in 20 ml of CH 2 C1 2 . Ethano!amine (297 NI, 4.92 mmol) was added, followed, in order, by EDCI (0.764 g, 4.92 mmol), l-hydroxybenzotriazole (0.665g, 4.92 mmol) and triethylamine (1.14 ml, 8.20 mmol) . The reaction was stirred at room temperature overnight. The reaction was quenched with NH 4 CI and extracted 3 times with ethyl acetate. The combined organic layer was then washed with saturated NaHCO 3 (aq.) and extracted 3 times with ethyl acetate. The organic layers were combined and washed with H 2 0 and extracted 3 times with ethyl acetate. The organic layers were combined and dried over Na 2 SO 4 and evaporated. The resulting residue was triturated with diethyl ether/hexane to obtain a solid, which was dried in vacuo to give a white solid (l.5g, 72%). IH NMR (300 MHz, CDCI 3 ) 6 7.93 (dd, J = 7.85, 1.61 Hz, IH), 7.65 (d, J = 1.61 Hz, IH), 7.62 (app q, J = 8.26 Hz, IH), 7.40 (d, J = 8.06 Hz, 1H), 7.39 - 7.30 (m, IH), 7.03 - 6.97 (m, IH), 6.88 - 6.81 (m, IH), 6.25 (s, IH), 5.20 (s, 2H), 3.70 - 3.52 (m, IH), 3.16 - 3.12 (m, 2H), 2.10 (S, 3H), 1.98 (s, 3H) ; ES-MS m/z 507 (M+H). ES-HRMS m/z 507.0719 (M+H calcd for C 23 H 22 BrF 2 N 2 0 4 requires 507.0726). Examples 488-491 The compounds of Examples 488-491-476 are prepared essentially according to the procedures set forth for Example 487. Compound% M+H ESHRMS No. R Yield MF Requires m/z Ex. 488NH ( CH 2 ) 2 OCH 3 84 C 24 H 24 BrF 2 N 2 0 4 528.0882 521.0868 Ex. 489-NHCH 3 79 C 22 H 20 BrF 2 NzO 477.0620 477.0602 Ex. 490-N (CH ) = 54 C 23 HH 2 BrF 2 N 2 0 491.G776 491.0753 Ex. 491-morpholine 65 C 2 sH 24 BrF 2 N 2 0 4 533.0858 533.0882 Example 492 F O HO 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-[5-(l-hydroxy-lmethylethyl)-2-methylphenyl]-6-methylpyridin-2(iH)-one Step i: Preparation of methyl 3- [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4methylbenzoate Methyl 3- [4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-4-methylbenzoate ( as prepared above) (l. Sg 0 4.51 mmol) was taken up in CH 2 C1 2 (I0 ml) . Nbromosuccinimide (0.80 g, 4.51 mmol) was added and the mixture stirred at room temperature for two hours. The CH 2 C1 2 is removed in vacuo and the residue is taken up in CH 3 CN. The resulting precipitate is collected on a filter pad and washed with CH 3 CN to yield a white solid 0.30 g, 14%, first crop). IH NMR (300 MHz, CDCI ) 6 8.06 (dd J = 8.06, 1.61 Hz, IH) , 7.80 (d, J = 1.61 Hz, 2H), 7.65 (app q, J = 8.46 Hz, IH), 7.48 (d, J = 8.06, IH) , 7.05 - 6.99 (m, IH) , 6.96 - 6.89 (m, IH) , 6.16 (s, IH), 5.31 (s, 2H), 3.93 (s, 3H), 2.17 (s, 3H), 1.96 (s, 3H) . ES-HRMS m/z 478.0476 (M+H calcd for C 2 HI BrF 2 NO 4 requires 478.0476). Step 2: Preparation of the title compound. Methyl 3-[3bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]-4-methylbenzoate (0.22 g, 0.46 mmol) was taken up in THF and cooled to 0°C. MeMgCI (3.0 M in THF) (0.73 ml, 2.2 mmol) was slowly added to the 0°C solution. The reaction was allowed to proceed without maintaining the 0°C bath temperature. The reaction was complete within two hours. At this time the mixture was quenched with saturated NH 4 CI (aq.) and extracted with ethyl acetate. The organic layers were combined, washed with H 2 0, and extracted with ethyl acetate. The organic layers were combined and dried over Na 2 SO 4 , filtered, and evaporated. The residue was taken up in 50% ethyl acetate/hexanes. The precipitate was collected on a filter pad and washed with ethyl acetate/hexanes to yield a white solid (0.i0 g, 45%) IH NMR (300 MHz, CD 3 OD) 6 7.70 (app q, J = 8.26, Hz, IH), (dd, J = 8.06, 2.01 Hz, IH), 7.40 (d, J = 1.81 Hz, IH), 7.12 7.06 (m, 2H) , 6.68 (s, IH) , 5.40 (s, 2H) , 2.05 (s, 3H) , (s, 3H), 1.57 (s, 6H). ES-HRMS m/z 478.0785 (M+H calcd C 23 H 23 BrF NO 3 requires 478.0824) . Example 493 O methyl 3- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin-I (2H) -yl] -4-methylbenzoate The title compound was prepared by taking up methyl 3-[4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4methylbenzoate (1.46g, 3.66 mmol) in dichloroethane (25 and adding N-chlorosuccinimide (0.49g, 3.66 mmol), dichloroacetic acid (catalytic), and heating to 50°C for hours. At this time, the solvent was removed in vacuo and residue taken up in diethyl ether. The precipitate collected on a filter pad. IH NMR (300 MHz, CDCI ) 6 8.07 J = 7.85, 1.61 Hz, IH), 7.80 (d, J = 1.81 Hz, 2H), 7.62 q, J = 8.46 Hz, IH), 7.48 (d, J = 7.85, IH), 7.05 - 6.95 IH), 6.93 - 6.89 (m, IH), 6.19 (s, IH), 5.30 (s, 2H), (s, 3H), 2.17 (s, 3H), 1.97 (s, 3H). ES-HRMS m/z 434.0932 calcd for C 22 HIgCIF 2 NO 4 requires 434.0965). Example 494 CI O OCH 3 methyl 4-[3-bromo-4-[(2,4-difluorobenzy])oxy]-6-methyl-2oxopyridin-l(2H)-yl]-3-chlorobenzoate Step i: Preparation of methyl 3-chloro-4-(4-hydroxy-6-methyl2-oxopyridin-l(2H)-yl)benzoate Cl OCH 3 4-Hydroxy-6-methyl-2-pyrone (24.5 g, 193.9 mmol) and methyl-3-amino-2-chlorobenzoate (30 g, 161.6 mmol) were suspended in 75 ml of 1,2-dichlorobenzene in a 250 ml, 3necked round bottom flask equipped with a J-Kem temperature controller probe, a Dean-Stark trap, and a heating mantle. The reaction was heated to 175°C for 20 minutes, during which, water and some 1,2-dichlorobenzene was collected in the DeanStark trap. The reaction was allowed to cool to about II0°C. At this point, 200 ml of toluene was added. The toluene mixture was allowed to stir for 72 hours at room temperature. A precipitate was collected on a filter pad. The precipitate was filtered and washed 3 times with toluene, 3 times with 50°C. water to remove excess pyrone, and dried in vacuo to give 1.81 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 294 (M+H) . Step 2: Preparation of methyl 3-chloro-4- [4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-!(2H)-yl]benzoate ,F CI OCH 3 Methyl 3-chloro-4-(4-hydroxy-6-methyl-2-oxopyridin-l(2H)- yl)benzoate ( from Step i) (2.4g, 8.17 mmol) was taken up in DMF (I0 ml). 2,4-difluorobenzylbromide (1.05 ml, 8.17 mmol) and K 2 C0 3 (1.13 g, 8.17 mmol) were added. The reaction stirred for 6 hours at room temperature. At this time, the reaction was poured into water (200 ml) and extracted with ethyl acetate. The ethyl acetate layer was dried over Na 2 SO 4 , filtered, and the solvent removed in vacuo to give amber oil (2.62 g, 77% crude yield). LC/MS, t= = 2.79 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 294 (M+H) . Step 3: Preparation of the title compound Methyl 3-chloro4- [4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]benzoate ( from step 2) (2.60g, 6.21 mmol) was taken up in CH 2 C1 2 (20 ml). N-bromosuccinimide (l.llg, 6.21 mmol) was added and the mixture stirred at room temperature for 4 hours. The CH 2 C1 2 is removed in vacuo and the residue is taken up in CH CN. The resulting precipitate is collected on a filter pad and washed with CHAIN to yield a white solid (0.75 g, 24%). IH 3H) . ES-HRMS m/z 497. 9892 (M+H calcd for C 2 HI 6 BrCIF 2 NO requires 497. 9914) . Example 495 F 3-bromo-4-[(2,4-difluorobenzyl)amino]-l-(3fluorobenzyl)pyridin-2(IH)-one Step 1 Preparation of 4-(benzyloxy)-l-(3-fluorobenzyl)pyridin-2(iH)- one OBn F A i00 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with 4-benzyloxy-2(iH)-pyridinone (20 g, 99.6 mmol) and N,N-dimethyl formamide (50 mL). K 2 CO 3 (13.7 g, 99.6 mmol) and KI ( 1.6 g, 9.6 mmol) were added followed by 3-fluorobenzyl bromide (14.6 mL, 119.4 mmol). The reaction mixture was heated for 18 h at 80 C. The reaction mixture was concentrated in vacuo and treated with hot ethyl acetate. The solids were filtered off, the filtrate was poured into water and was extracted with ethyl acetate. The organic extract was washed with brine, dried with anhydrous Na 2 SO and concentrated in vacuo. The residue was dissolved in hot ethyl acetate and precipitated with hexanes to give the title compound (i0 g, 33%). IH NMR (400 MHz, CD 3 OD) 7.57 (d, J = 8.4 Hz, IH), 7.37 (m, 5H), 7 07 (d, J = 8.4 Hz, !H), 7.01 (app d, J = 8.4 Hz, 2H), 6.17 (d J = 2.68 and 7.6 Hz, IH), 6.04 (d, J = 2.68 Hz, IH) , 5.10 s, 2H) , 5.08 (s, 2H) ppm. F NMR (400 MHz, CD 3 OD) 6 -114.88 (I F) ppm. ES-HRMS m/z 310.1271 (M+H calcd for C 19 HIvFNO 2 requires 310.1238). Step 2 Preparation of i- (3-fluorobenzyl)-4-hydroxypyridin-2(IH)-one OH F A small Parr bottle was charged with SC-82484 (i0 g, 32.3 mmol), ethanol (175 mL) andl0% Pd/C (0.5 g). The system was flushed twice with both nitrogen and hydrogen. The reaction mixture was hydrogenated at 30 psi until no starting material was visible by LC-MS. The reaction mixture was slurried with Celite and then was filtered through a pad of celite. The filtrate and ensuing ethanol washes were concentrated in vacuo to give a beige solid. IH NMR (400 MHz, CD 3 OD) 6 7.53 (d, J = -115.33 (I F) ppm. ES-HRMS m/z 218.0641 (M+H calcd for CI 2 HnFNO 2 requires 218.0612). Step 3 Preparation of 4-[(2,4-difluorobenzyl)amino]-l-(3fluorobenzyl)pyridin-2(iH)-one F F The product from Step 2 (0.5 g, 2.28 mmol) and 2,4difluoro benzylamine (4 mL, 33.6 mmol) were combined in a nitrogen flushed culture tube. The tube was capped and heated at 180 C for 24 h. The excess amine was distilled in vacuo and the residue was chromatographed on silica (95:5 ethyl acetate: methanol). The final compound was isolated as a light yellow solid (0.16 g, 36%). IH NMR (400 MHz, CD 3 OD) 8 7.33 (m, 3H), 7.03 (d, J = 8 Hz, IH) , 6.96 (m, 3H), 6.95 (m, IH), 5.97 (dd, J = 3.2 and 8.0 Hz, 1 H), 5.48 (d, J = 2.56 Hz, IH), 5.02 (s, 2H), 4.33 (s, 2H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6-113.88 (I F), -115.33 (IF), -116.78 (IF) ppm. ES-HRMS m/z 345.1221 (M+H calcd for C 19 HIvF 3 N 2 0 requires 345.1209). Step 4 Preparation of 3-bromo-4-[(2,4-difluorobenzyl)amino]-l- (3-fluorobenzyl)pyridin-2(IH)-one N-Bromo succinimide (81 mg, 0.46 mmol) was added to a solution of the product from Step 3 (0.15 g, 0.44 mmol) in methylene chloride (I0 mL) . After stirring at 25 C for 1 h, the reaction was complete by LC-MS. The reaction mixture was poured into saturated aqueous NaHCO 3 . The aqueous mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried with anhydrous MgSO 4 , and concentrated in vacuo. IH NMR (400 MHz, CDCI]) 6 7.3-7.2 (m, 4H), 7.07 (app J = 7.6 Hz, 2H) , 6.97 (m, 2H) , 6.80 (m, 2H) , 5.78 (d, J = 7.6 Hz, IH), 5.30 (br s, IH), 5.08 (s, 2H), 4.46 (d, J = 6 Hz, ppm. 19 F NMR (400 MHz, CDCI 3 ) 6 -110.64 (I F), -112.75 (IF), 114.79 (IF) ppm. ES-HRMS m/z 423.0275 (M+H calcd for CI HIsBrF 3 N 2 0 requires 423.0314) . Example 496 F3C NH .Br F 3-bromo-l- (3-fluorobenzyl)-4-{ [3- (trifluoromethyl) benzyl] amino]pyridin-2 (IH) -one The title compound was prepared essentially as in Example 495. IH krMR (400 MHz, CDCIs) 6 7.54 (m, 2H), 7.48 (m, 2H), 7.27 (q, J = 3.1, 9.0 Hz, IH), 6.96 (app t, J = 8.8 Hz, 2H), 5.71 (d, J = 7.6 Hz, IH), 5.4 (br m, IH), 5.08 (s, 2H), 4.52 (d, J = 5.6 Hz, 2H) ppm. 9 F NMR (400 MHz, CDCI 3 ) 5 -63 (3 F), -112 (i F) ppm. ES-HRMS m/z 455.0388 (M+H calcd for C 20 HI 6 BrF 4 N 2 0 requires 455.0377) . Example 497 F 3 - bromo1 - ( 3 - f luorobenzyl ) - 4 - { [ 4 - f luoro - 2 - ( t ri f luoromethyl ) benzyl ] amino } pyridin2 (IH) - one The title compound was prepared essentially as in Example 495. IH NMR (400 MHz, CDCI ) $ 7.43 (m, 2H), 7.27 (m, 3H), 7.07 (m, 2H), 6.99 (m, 2H), 5.65 (d, J = 10Hz, IH] , 5.46 (br s, IH), 5.09 (s, 2H), 4.64 (s, 2H) ppm. 19 F NMR (400 MHz, CDCI 3) 6-61.31 (3 F), -112.69 (i F), 112.97 (IF) ppm. ES-HRMS m/z 473.0246 (M+H calcd for C 20 H:sBrFsN 2 0 requires 473.0282). Example 498 Preparation of -bromo-4- [(4-chloro-2-fluorobenzyl)amino]-l- (3fluorobenzyl) pyridin2 (1H) -one The LiLle compound was prepared essentially as in Example 495. H N'MR 400 MHz, CDCI 3 ) 6 7.27 (m, IH), 7.19 (app t, J = 8.8 Hz, IH), 7.10 (m, 4H), 6.95 (app t, J = 8.8 Hz, 2H), 5.74 (d, J = 8 Hz IH), 5.40 (br s, IH), 5.08 (s, 2H), 4.47 (d J = 6 Hz, 2H) ppm. z9 F NMR (400 MHz, CDCI 3 ) 6-112.67 (i F), - 116.39 (i F) ppm. ES-HRMS m/z 439.0047 (M+H calcd for C 19 HIsCIBrF 2 N 2 0 requires 439.0019). Example 499 F NH -N- "O F The title compound was prepared essentially as in Example 495. 1H NNR (400 NHz, CDC1 3 ) 6 7.357.2 (m, 1H), 7.27 (dd, J = 2.5 and 8 ttz, 1H), 7.05 (app d, J = 7.2 Hz, 3H), 6.97 (m, 4H), 5.72 (d, J = 7.6 Hz, 1H), 5.41 (br s, 1H), 5.08 (s, 2H), 4.46 (d, J = 6.4 Hz, 2H) ppm. 19 F NMR (400 MHz, CDCI 3 ) 6 -112.5 (i F), -113 (i F) ppm. ES-HRMS m/z 405.0431 (M+H calcd for C 19 HI 6 BrF 2 N O requires 405.0409). Example 500 ,8r F D Preparation of 3-bromo-4-[(2,4-difluorobenzyl)amino]-6-methylI- (pyridin-4-ylmethyl) pyridin-2 (IH) -one Step 1 Preparation of 4-[(2,4-difluorobenzyl)amino]-6-methyll-(pyridin-4-ylmethyl)pyridin-2(iH)-one F (0.3 g, 1.39 mmol) and 2,4-difluoro benzylamine (I mL, 8.4 mmol) were combined in a nitrogen flushed culture tube. The tube was capped and heated at 180 C for 24 h° The excess amine was distilled in vacuo. IH NMR (400 MHz, CD 3 OD) 5 8.44 (dd, J = 1.7 and 4.SHz, 2H), 7.38 (q, j = i0 and 15 Hz, IH), 7.14 (d, J = 4.8 Hz, 2H), 6.95 (m, 2H), 5.90 (dd, J = 1 and 2.5Hz, IH), 5.47 (d, J = 2, IH), 5.28 (s, 2H), 4.33 (s, 2H), 2.27 (s, 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6 -113.73 (I F), 116.66 (i F) ppm. ES-HRMS m/z 342.1422 (M+H calcd for C 19 HIBF 2 N 3 0 requires 342.1418) . Step 2 Preparation of 3-bromo-4- [(2,4-difluorobenzyl)amino]-6methyl-l-(pyridin-4-ylmethyl)pyridin-2(IH)-one N-Promo succinimide (77 mg, 0.43 mmol) was added to a solution of the product of Step 1 (0.14 g, 0.41 retool) in methylene chloride (i0 mL) . After stirring at 25 C for 1 h, the reaction was complete by LC-MS. The reaction mixture was poured into saturated aqueous NaHCO 3 . The aqueous mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried with anhydrous Na 2 SO 4 , filtered and concentrated in vacuo. The residue was triturated with hexanes to give the title compound as a yellow solid (81 mg, 47 %). zH NMR (400 MHz, CDCI 3 ) 8.47 (dd, J = 1.6 and 4.8Hz, 2H) , 7.24 (q, J = 6.4 and 13.6 Hz, IH) , 7.01 (d, J = 6.4 Hz, 2H) , 6.83 (m, 2H), 5.68 (s, IH), 5.25 (s, 2H), 4.45 (d, J = 6.4Hz, 2H), 2.12 (s, 3H) ppm. 19 F NMR (400 MHz, CDCI ) 6110.51 (m, 1 F), -114.66 (m, I F) ppm. ES-HRMS m/z 420.0524 (M+H calcd for C 19 HIvBrF 2 N 3 0 requires 420.0523). Example 501 Preparation of 3-bromo-4- [ (2,4-difluorobenzyl)amino]-6-methylThe title compound was prepared essentially as in Example 500. IH NMR (400 MHz, CDCI 3 ) 8 8.45 (d, J = 4.8Hz, 2H), 7.55 (app t, J = 6 Hz, IH), 7.21 (m, 2H), 6.83 (m, 2H), 5.65 (s, IH , 5.34 (d, J = 5.2Hz, !H), 5.27 (s, 2H , 4.45 (s, 2H), 2.10 (d J = 4.SHz, 3H) ppm. 19 F NMR (400 MHz CDCI 3 ) 6-1!0.74 F) -114.86 (I F) ppm. ES-HRMS m/z 420.0533 (M+H calcd for CIgHITBrF 2 N 3 0 requires 420.0523). Example 502 .Br F Preparation of 3-bromo-4-[(2,4-difluorobenzyl)amino]-l-(2,6difluorophenyl)-6-methylpyridin-2(IH)-one Step 1 Preparation of 4-[(2,4-difluorobenzyl)amino]-l-(2,6difluorophenyl)-6-methylpyridin-2(IH)-one F l-(2,6-difluorophenyl)-4-hydroxy-6-methylpyridin-2(IH)- one (0.3 g, 1.26 mmol) and 2,4-difluoro benzylamine (ImL, 8.4 mmol) were combined in a nitrogen flushed culture tube. The tube was capped and heated at 180 C for 24 h. The excess amine was distilled in vacuo and the residue was chromatographed on silica (i:i hexanes: ethyl acetate). The compound was approximately 50% pure and was carried on without further purification (0.633 g) . IH NMR (400 MHn, CD 3 OD) 6 7.53 (m, IH), 7.41 (m, IH), 7.16 (t, J = 8.SHz, 2H), 6.93 (m, 2H), 6.00 (s, IH), 5.42 (s, IH), 5.42 (s, ill), 4.37 (s, 2H), 1.93 (s, 3H) ppm. LC/MS, tr = 4.65 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 363 (M+H) . Step 2 Preparation of 3-bromo-4-[(2,4-difluorobenzyl)amino]-l- (2,6-difluorophenyl -6-methylpyridin-2(iH)-one N-Bromo succinimide (168 mg, 0.945 mmol) was added to a solution of the product of Step 1 (0.633 g) in methylene chloride (i0 mL). After stirring at 25 C for 1 h, the reaction was 50 % complete by LC-MS. Additional N-bromo succinimide (150 mg) was added and the reaction was stirred at C for 12 h. The reaction mixture was poured into saturated aqueous NaHCO The aqueous mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried with anhydrous Na 2 SO 4 , and concentrated in vacuo. The residue was purified by reverse phase chromatography (60:40 Acetonitrile: water with 0.05% trifluoroacetic acid). The title compound was isolated as the TFA salt (0.161g, 23%). IH NMR (400 MHz, ES-HRMS m/z 441.0231 (M+H calcd for C 19 HI 4 BrF N 2 0 requires 441.0220). Example 503 Preparation of 3-chloro-4-[(2,4-difluorobenzyl)amino]-l-(2,6difluorophenyl)-6-methylpyridin-2(IH)-one l-(2,6-difluorophenyl)-4-hydroxy-6-methylpyridin-2(IH)- one (0.3 g, 1.26 mmol) and 2,4-difluoro benzylamine (ImL, 84 mmol) were combined in an nitrogen flushed culture tube. The tube was capped and heated at 180 C for 24 h. The excess amine was distilled in vacuo and the residue was used without further purification. N-Chloro succinimide (168 mg, 1.26 mmol) was added to a solution of the residue in methylene chloride (i0 mL). After stirring at 25 C for 1 h, the reaction mixture was poured into saturated aqueous NaHCO 3 . The aqueous mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried with anhydrous Na 2 SO 4 , and concentrated in vacuo. The residue was chromatographed on silica (25:75 hexanes: ethyl acetate) to give the title compound (32 rag, 6%). IH NMR (400 MHz, CD 3 OD) 6 7.55 (m, IH), (IF) ppm. ES-HRMS m/z 397.0752 (M+H calcd for CigHi 4 CIF 4 N=O requires 397.0725) . Example 504 GN Preparation of 3-{ [3-chloro-4-[(2,4-difluorobenzyl)amino]-6methyl-2-oxopyridin-l(2H)-yl]methyl}benzonitrile Step 1 Preparation of 3-phthalimidomethyl-benzonitri!e NC i 'NPh 3-Phthalimidomethyl-benzonitrile was prepared as described the literature. (Bookser, B.C.; Bruice, T.C. J. Am. Chem. Soc. 1991, 113, 4208-18.) Step 2 Preparation of 3-(aminomethyl)benzonitrile NC "NH 2 3-(Aminomethyl)benzonitrile was prepared as described in the literature. (Bookser, B.C.; Bruice, T.C. J. Am. Chem. Soc. 1991, 113, 4208-18.) Step 3 Preparation of 3-[(4-hydroxy-6-methyl-2-oxopyridinl(2H)-yl)methyl]benzonitrile A nitrogen flushed pyrex reaction tube was charged with 3-(aminomethyl)benzonitrile (i g, 7.9 mmol), 4-hydroxy-6methyl-2-pyrone (I g, 7.9 mmol) and water (20 mL). The tube was capped and was heated to reflux. After 1.5 h, the product precipitated from solution. The reaction mixture was cooled to room temperature, filtered and washed with water. The product was used without further purification (1.67g, 88 %). IH N-MR (400 MHz, dmso-d 6 ) 6 10.53 (s, IH), 7.61 (d, J = 8Hz, IH) , 7.52 (t, J = 8Hz, 2H) , 7.38 (d, J = 8 Hz, IH) , 5.79 (dd, J = 1 and 2.5 Hz, IH) , 5.56 (d, J = 2.7 Hz, IH) , 5.18 (s, 2H) , 2.14 (s, 3H) ppm. ES-HRMS m/z 241.0968 (M+H calcd for C 14 HI 3 N 2 0 2 requires 241.0972). Step 5 Preparation of 3-{ [4-[(2,4-difluorobenzyl)amino]-6methyi-2-oxopyridin-l(2H)-yl]methyl}benzonitrile F The product from Step 4 (0.5 g, 2.08 mmol) and 2,4-difluoro benzylamine (2mL, 16.8 mmol) were combined in a nitrogen flushed culture tube. The tube was capped and heated at 180 C for 24 h. The excess amine was distilled in vacuo and the residue was triturated with ethyl acetate/ hexanes to precipitate the starting materials. The residue was chromatographed on reverse phase (I:i water: acetonitrile with 0.05% trifluoroacetic acid ). The product of Step 5 was isolated as a white semi-solid (0.125g, 15%). IH NMR (400 CD 3 OD) 6 7.61(d, J = 8Hz, IH}, 7.49 (t, J = 8 Hz, !H), 7.41 3H), 6.94 (m, 2H) , 5.89 (dd, J = 0.8 and 2.7Hz, ill), 5.47 (d, J = 2.SHz, IH) , 5.27 (s, 2H), 4.34 (s, 2H) , 2.18 (s, 3H) ppm. LC/MS, tr = 4.87 minutes (5 to 95% acetonit 1 -ile/water over minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 366 (M+H) . Step 6 Preparation of 3-{ [3-chloro-4-[(2,4difluorobenzyl) amino] - 6-methyl-2-oxopyridin1 (2H) - yll methyl }benzonitrile Z CN N-Chloro succinimide (36 mg, 0.27 mmol) was added to a solution of the product of Step 5 (0.125 g, 0.26 mmol) in methylene chloride (I0 mL). After stirring at 25 C for 2 h, the reaction was complete by LC-MS. The reaction mixture was poured into saturated aqueous NaHCO The aqueous mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried with anhydrous Na 2 SO and concentrated in vacuo. The residue was triturated with acetonitrile to give the title compound as a tan solid (20 mg, 13%). IH NMR (400 ppm. LC/MS, tr = 5.49 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50°C). ESMS m/z 400 (M+H) . Example 505 F Preparation of 4-{ [3-chloro-4-[(2,4-difluorobenzyl)amino]-6methyl-2-oxopyridin-l(2H)-yl]methyl}benzonitrile The title compound was prepared essentially as in Example 504. IH NMR (400 MHz, CD 3 OD) 6 7.66 (d, J = 8 Hz, 2H), 7.33 (q, J =8 and 15.2 Hz, IH), 7.25 (d, J = 8 Hz, 2H), 6.94 (m, 2H), 6.01 (s, IH), 5.36 (s, 2H), 4.55 (s, 2H), 2.19 (s, 3H} ppm. 19 F N-MR (400 MHz, CODED) 6 -77.52 (IF), -113.89 (I F), - 116.71 (i F) ppm. LC/MS, tr = 5.49 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 400 (M+H) . Example 506 .Br F .OH Preparation of 3-bromo~4- [(2,4-difluorobenzyl)oxy]-l- [2fluoro5 - ( hydroxyme t hyl ) phenyl ] - 6 -methylpyridi n2 (IH) -one Step i Preparation of (3-amino-4-fluorophenyl)methanol NH 2 A flask equipped with overhead stirrer was charged with 4-fluoro-3-nitrobenzyl alcohol (20g, 0.117 mol} and 200 mL of 5:1 isopropanol: water. Ammonium chloride (62 g, 1.17 mol) was added followed by iron filings (65g, 1.17 mol) . The mixture was stirred at 70 C for 1.5 H when it was shown to be complete by LC-MS. The liquid was decanted and the solids were washed with additional isopropanol: water. The isopropanol was removed and the residue was diluted with 0.5 HCI and was extracted with ethyl acetate. The aqueous layer was brought to pH 12-14 with 2.5 N NaOH and was extracted with ethyl acetate. The organic layer was dried with anhydrous Na 2 SO 4 and concentrated in vacuo. 3-Amino-4-fluorophenyl methanol was isolated as a brown solid (4.5g, 27%) and was used without further purification. LC/MS, tr = 2.40 minutes to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 142 (M+H). ES-HRMS m/z 142.0692 (M+H calcd for CTHsFNO requires 142.0663). Step 2 Preparation of l-[2-fluoro-5-(hydroxymethyl)phenyl]-4hydroxy-6-methylpyridin-2(iH)-one A i00 mL round bottomed flask equipped with stirbar, Dean-Stark trap and reflux condensor was charged with (3amino-4-fluorophenyl)methanol (4.5 g, 31.9 mmol), 4-hydroxy-6-methyl-2-pyrone (4 g, 31.9 mmo!) and o- dichlorobenzene (5 mL) . The system was immersed in a 170 C oil bath for i0 minutes. The solvent was removed in vacuo and the residue was chromatographed on reverse phase (75:25 water:acetonitrile with 0.05% TFA). The product contained some starting materials after purification and was used without further purification (1.27g, 15%). IH N-MR (400 MHz, dmso-d 6) 5 7.39 (m, IH), 7.20 (dd, J = 2.2 and 7.6 Hz, IH) , 6.74 (dd, J = 2.7 and 9.6 Hz, IH), 5.93 (dd, J = 1.2 and 2.2 Hz, IH), 5.22 (dd, J = 0.4 and 2.2 Hz, IH), 2.12 (s, 3H) ppm. ES-HRMS m/z 250.0862 (M+H calcd for C: 3 HI 3 FNO requires 250.0874). Step 3 Preparation of 4-[(2,4-difluorobenzyl)oxy]-l- [2-fluoro5-(hydroxymethyl)phenyl]-6-methylpyridin-2(iH)-one F OH A i00 mL roundbottomed flask (nitrogen purged) was charged with l- [2-fluoro-5-(hydroxymethyl)phenyl]-4-hydroxy-6methylpyridin-2(IH)-one (l.2g, 4.82 mmol) and N,N-dimethyl formamide (i0 mL). Potassium carbonate (0.6g, 4.4 mmol) and 2,4-difluorobenzyl bromide (0.56 mL, 4.4 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with saturated aqueous NaHCO and extracted with ethyl acetate. The organic layer was concentrated in vacuo and the residue was chromatographed on silica (9:1 methylene chloride: ethanol). The impure oil (0.3g, 17%) was carried on without further purification. IH NMR (400 MHz, CD 3 OD) 6 7.54 (m, 2H), 7.30 (m, 2H) , 7.02 (m, 2H) , 6.17 (dd, J = 1 and 2.8 Hz, IH) , 6.03 (d, J = 2.8 Hz, IH) , 5.14 (s, 2H) , 4.62 (s, 2H), 2.14 (s, 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6 -111.35 (IF), -115.97 (i F) , -127.31 (I F) ppm. LC/MS, tr = 5.05 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 375 (M+H) . Step 4 Preparation of 3-bromo-4- [(2,4-difluorobenzyl)oxy]-l- [2 - f luoro5- (hydroxymethyl) phenyl ] - 6 -methylpyridin2 (IH) -one F OH N-Bromo succinimide (50 mg, 0.3 mmol) was added to a solution of the product of Step 3 (0.12 g, 0.32 mmol) in N,Ndimethyl formamide (4 mL). After stirring at 25 C for 2 h, trifluoroacetic acid (50 ML) was added. After 1 h, additional N-Bromo succinimide (30 mg) was added. After 1 h, the reaction was complete by LC-MS. The reaction mixture was poured into brine and was extracted with ethyl acetate. The organic layer was washed with brine, dried with anhydrous Na 2 SO 4, and concentrated in vacuo. The residue was chromatographed on reverse phase (95:5 methylene chloride: ethanol). The title compound was isolated as the TFA salt (38 115.92 (I F), -127.23 (i F) ppm. ES-HRMS m/z 454.0228 (M+H calcd for C 20 H 6 BrF 3 NO 3 requires 454.0260). Example 507 F CO 2 H Preparation of 3- [3-chloro-4- [(2,4-difluorcbenzyl)oxy]-6methy!-2-oxopyridin-l(2H) -yl]-4-f!uorobenzoic acid Step 1 Preparation of methyl 4-fluoro-3-nitrobenzoate NO 2 CO 2 Me A 1 L 3-necked round bottomed flask equipped with a nitrogen inlet, stirbar, addition funnel and thermocouple was charged with 4-fluoro-3-nitrobenzoic acid (50 g, 0.27 mol) and methanol (300 mL). The system was cooled to 0 C and acetyl choride (27 mL, 0.37 mol) was added dropwise. The system was warmed to room temperature, the addition funnel was replaced with a reflux condensor, and was heated to reflux for 1.5 h. The reaction mixture was cooled to room temperature, quenched with saturated aqueous NaHCO and extracted with ethyl acetate. The organic extract was washed with brine, dried with Na 2 SO 4 and concentrated in vacuo to give methyl 4-fluoro3-nitrobenzoate as an orange solid (40.6 g, 75%) . IH NMR (400 Hz, IH), 3.94 (s, 3H) ppm. ES-HRMS m/z 200.02446 (M+H calcd for CBHTFN0 4 requires 200.0354). Step 2 Preparation of methyl 3-amino-4-fluorobenzoate NH 2 F 3 2 Me A Parr bottle was charged with the product of SEep 1 (40 g, 0.2 mol), ethanol (400 mL) andl0% Pd/C (I g g). The system was flushed twice with nitrogen and hydrogen. The reaction mixture was hydrogenated at 40 psi until no starting material was visible by LC-MS. The reaction mixture was slurried with Celite and then was filtered through a pad of celite. The filtrate and ensuing ethanol washes were concentrated in vacuo to give methyl 3-amino-4-fluorobenzoate as an orange solid (30.6 g, 91%). IH NMR (400 MHz, CD 3 OD) 6 7.54 (d, J = 8.7 Hz, IH), 7.35 (m, IH), 7.06 (t, J = 8.7 Hz, IH), 3.09 (s, 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6 -131.02 (IF) ppm. ES-HRMS m/z 199.0281 (M+H calcd for CsHTFNO 4 requires 199.02) . Step 3 Preparation of methyl 4-fluoro-3-(4-hydroxy-6-methyl-2oxopyridin-l(2H)-yl)benzoate OH CO 2 Me A 250 mL round bottomed flask equipped with stirbar, Dean-Stark trap and reflux condensor was charged with the product of Step 3 (30 g, 0.18 mol), 4-hydroxy-6-methyl-2pyrone (22.6 g, 0.18 mol), and o-dichlorobenzene (90 mL). The system was immersed in a 170 C oil bath for 30 minutes and was then cooled to room temperature. The reaction mixture was washed with aqueous Na 2 CO 3 (38 g, 0.36 mol, 300 mL water). The aqueous layer was washed with ethyl acetate and then was acidified to pH 1-2 with concentrated HCI. This was extracted with ethyl acetate, which was then dried with MgS0 4 and concentrated in vacuo. The viscous orange oil was used without further purification (14.4 g, 28%). H NMR (400 MHz, CD 3 OD) 6 8.18 (dddd, J = 2.3, 5.2, 7.2 and 8.8 Hz, IH) , 7.97 (dd, J = 2 and 7.2 Hz, IH) , 7.44 (t, J = 8.8 Hz, IH), 6.09 (d, J = 1.8 Hz, IH), 5.78 (d, J = 2.4 Hz, IH), 3.9 (s, 3H), 2.14 (s, 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 5-117.29 (IF) ppm. ES-HRMS m/z 278.0796 (M+H calcd for C 14 HI 3 FNO 4 requires 278.0823). Step 4 Preparation of methyl 3-[4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]-4-fluorobenzoate F FALCON 2 M e A I00 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the product of Step 3 (14.4 g, 51.9 mmol) and N,N-dimethyl formamide (40 mL). 1,8diazabicyclo[5.4.0]undec-7-ene (10.9 mL, 72.8 mmol) was added followed by 2,4-difluorobenzyl bromide (9.3 mL, 72.8 mmol). The reaction mixture was stirred at 65 C for 18 h, was poured into saturated aqueous NaHCO 3 and was extracted with ethyl acetate. The organic layer was washed with brine, dried with Na 2 SO 4 and concentrated in vacuo to give the title product, as an orange oil (21.5g), which was carried on to the next reaction without further purification. IH NMR (400 MHz, CD 6 8.20 (dddd, J = 2.2, 4.8, 7.2 and 8.8 Hz, IH), 8.00 (dd, 2.2 and 7.2 Hz, IH), 7.56 (td, J = 2.4, 6.4 and 9.2 Hz, IH), 7.46 (t, J = 9.2 Hz, IH), 7.02 (m, 2H), 6.18 (dd, J = 0.8 2.6 Hz, IH), 6.04 (d, J = 2.7 Hz, IH), 5.14 (s, 2H) , 3.90 3H), 1.98 (s, 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6 -111.34 (IF) , -116.00 (i F), -117.35 (i F) ppm. ES-HRMS m/z 404.1104 (M+H calcd for C 21 HIvF NO 4 requires 404.1104). Step 5 Preparation of methyl 3-[3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4fluorobenzoate F F GO 2 M e A 250 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the product of Step 4 (21 g, 52 mmol) and N-methyl-2-pyrrolidine (i00 mL). N-Chloro succinimide (8.3 g, 62 mmol) was added and the reaction mixture was stirred at 65 C for 2 h. The mixture was then cooled to room temperature, poured into saturated aqueous NaHCO 3 and extracted with ethy! acetate. The organic layer washed with brine, dried with Na 2 SO 4 , and concentrated in vacuo. The residue was triturated with diethyl ether and filtered to give the title compound, as a white powder (5.9 (i F) ppm. ES-HRMS m/z 438.0723 (M+H calcd for C 21 HI CIF 3 NO 4 requires 438. 0714) . Step 6 Preparation of 3-[3-chloro~4-[(2,4-difluorobenzyl)oxy]- 6_methyi-2_oxopyridin-l(2H)~yl]-4-fluorobenzoic acid F 2 H A i00 nil round bottomed flask was charged with the product of Step 5 (2.5 g, 5.72 mmol), tetrahydrofuran (40 mL), methanol (i0 mL), and water (I0 mL) . To this slurry was added 2.5 N NaOH (4.6 mL, 11.4 mmol). The reaction mixture became clear after 5 minutes and the reaction was complete in minutes by LC-MS. The organics were removed on the rotary evaporator and the remaining solution was acidified to pH 3 with 6N HCI. The desired compound was precipitated by the addition of diethyl ether and subsequent filtration. The title compound was isolated as a white powder (2.5 g, 98%). IH NMR (400 MHz, dmso-d 6 ) 6 8.10 (dddd, J = 2.1, 4.8, 7.2 and 8.4 Hz, IH), 8.00 (dd, J = 2.1 and 7.6 Hz, IH), 7.66 (q, J = 9.2 and 15.6 Hz, IH), 7.57 (t, J = 8.8 Hz, IH), 7.34 (td, J = 2.4 and 10.4 Hz, IH), 7.17 (tdd, J = i, 2.7 and 8.4 Hz, IH), 6.76 (s, IH), 5.33 (s, 2H), 1.98 (s, 3H) ppm. 19 F NMR (400 MHz, dmso-d 6) 6 -109.32 (IF), -113.64 (i F), -117.22 (I F) ppm. ES-HRMS m/z 424.0575 (M+H calcd for C 20 HI 4 CIF 3 N0 4 requires Example 508 I Preparation of 3- [3-chloro-4- [(2,4-difluorcbenzyl)oxy]-6methyl-2-oxopyridin-i (2H) -yl] -4fluoro-N-methylbenzamide To a reaction vessel (borosilicate culture tube) was added 3-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-4-fluorobenzoic acid (0.300 g, 0.708 mmol) and l-hydroxybenzotriazole (0.048 g, 0.45 mmol) . N,NDimethylformamide (3 mL) was added to the reaction vessel followed by approximately 1.2 g of the polymer bound carbodiimide resin (1.38 mmol/g) . Additional N,Ndimethylformamide (2 mL) was then added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker at approximately 200 RPM at room temperature for 15 minutes. N-Methyl amine (I mL, 2 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with tetrahydrofuran (20 mL) and treated with approximately 2.17 g of polyamine resin (2.63 mmol/g) and approximately 2.8 g of methylisocyanate functionalized polystyrene (1.5 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature for 3 hours. The reaction vessel was then opened and the solution phase product was separated from the insoluble quenched byproducts by filtration and collection into a vial. After partially evaporation the insoluble byproducts were rinsed with tetrahydrofuran (2 x i0 mL). The filtrate was evaporated by blowing N 2 over the vial and the resulting solid was triturated with diethyl ether to give an off-white solid. (0.168 g, 59%) iH NMR (400 MHz, CODED) 6 8.02 (dddd, J = 2, 4.4, 7.2 and 8.4 Hz, IH), 7.80 (dd, J = 2 and 6.8 Hz, IH), 7.62 (q, J = 8 and 14.4 Hz, IH), 7.34 (t, J = 8.8 Hz, IH), 7.04 (m, 2H), 6.69 (s, IH) , 5.36 (s, 2H) , 3.29 (s, 3H) , 1.98 (s, 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 5-108.94 (IF), -113.55 (i F), -117.76 (I F) ppm. ES-HRMS m/z 437.0861 (M+H calcd for C IHITClF 3 N 2 0 3 requires 437.0874) . Examples 509-518 , By following the method of Example 508 and replacing Nmethylamine with the appropriate amine, the compounds of Examples 509-518 are prepared. Example% M+H ES RMS No. R 1 R 2 Yield MF Requires m/z Example 519 .Br F CO 2 H Preparation of 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]-4-fluorobenzoic acid Stepl Preparation of methyl 3-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4fluorobenzoate F ,Br F F CO 2 Me A i00 mL round bottomed flask equipped with stirbar nitrogen inlet was charged with methyl 3-[4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4fluorobenzoate (7.3 g, 18 mmol) and N-methyl-2-pyrrolidine (20 mL). N-Bromo succinimide (3.5 g, !9.8 mmol) was added and the reaction mixture was stirred at room temperature for minutes. The mixture poured into saturated aqueous NaHCO 3 and extracted with ethyl acetate. The organic layerwas washed with brine, dried with Na 2 SO 4 , and concentrated in vacuo. The residue was triturated with diethyl ether and filtered to give the title compound as a white powder (3.49 g) . IH NMR (400 MHz, CD 3 OD) 6 8.16 (qd, J = 3, 6.8 and 15.6 Hz, IH), 7.84 (d, J = 2.12 Hz, IH), 7.64 (q, J = 8.4 andl4.8 Hz, IH), 7.29 (d, J = 8.4 Hz, IH), 7.04 (m, 2H), 6.60 (s, IH), 5.34 (s, 2H), 3.87 (s, 3H), 2.00 (s, 3H) ppm. "9 F NMR (400 MHz, CD 3 OD) 6-111.51 (IF) , -115.98 (IF), -117.43 (IF)ppm. ES-HRMS m/z 494.0387(M+H calcd for C 22 H gBrF 2 NOs requires 494.0409). Step 2 Preparation of 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]-4-fluorobenzoic acid F .Br F CO 2 H A i00 niL round bottomed flask was charged with the product of Step 2 (3.4 g, 7.05 mmol), tetrahydrofuran (40 mL), methanol (i0 mL), and water (I0 mL). To this slurry was added 2.5 N NaOH (5.6 mL, 14.1 mmol). The reaction mixture became clear after 5 minutes and the reaction was complete in 1 h by LC-MS. The organics were removed on the rotary evaporator and the remaining solution was acidified to pH 1-2 with 6N HCI. The desired compound was precipitated by the addition of water and diethyl ether and subsequent filtration. The title compound was isolated as a white powder (2.64 g, 80%). IH N-MR (400 MHz, CD 3 OD) 6 8.21 (dddd, J = 2.4, 5.2, 7.2 and 9.2 Hz, !H), 8.00 (dd, J = 2.0 and 7.2 Hz, IH), 7.65 (q, J = 8.4 and 14.8 Hz, IH), 7.45 (t, J = 8.4 Hz, IH), 7.04 (appt, J = 9.6 Hz, IH), 6.65 (s, IH), 5.36 (s, 2H), 2.07 (s, 3H) ppm. 9 F NMR (400 MHz, CD 3 OD) 6 -111.40 (IF) , -116.00 (! F) , -118.36 F) ppm. ES-HRMS m/z 480.0259 (M+H calcd for C 21 HITBrF 2 NOs requires 480. 0253) . Example 520 Br F MeO c 02 H Preparation of 3- [3-bromo-4- [(2,4-difluorobenzyl)oxy] -6methyl-2-oxopyridin-i (2H) -yl] -4-methoxybenzoic acid Step 1 Preparation of methyl 3-amino-4-methoxybenzoate NH 2 MeO cO 2 Me A 1 L 3-necked round bottomed flask equipped with a nitrogen inlet, stirbar, addition funnel and thermocouple was charged with 3-amino-4-methoxy benzoic acid (50 g, 0.299 mol) and methanol (300 mL) . The system was cooled to 0 C and acetyl choride (30 mL, 0.42 mol) was added dropwise. The system was warmed to room temperature, the addition funnel was replaced with a reflux condensor, and was heated to reflux for 1.5 h. The reaction mixture was cooled to room temperature, quenched with saturated aqueous NaHCO and extracted with ethyl acetate. The organic extract was washed with brine, dried with Na 2 S0 4 and concentrated in vacuo to give methyl 3amino-4-methoxybenzoate as a dark solid (47.9 g, 88%). IH NMR (400 MHz, CD 3 OD) 6 7.40 (t, J = 2 68 Hz, IH), 7.37 (t, J = 2.0 Hz, IH) , 6.86 (d, J = 8.8 Hz, IH) , 3.98 (s, 3H) , 3.81 (s, 3H) ppm. ES-HRMS m/z 182.0826 (M+H calcd for CgHI=CIN0 3 requires 182.0812) . Step 2 Preparation of methyl 3-(4-hydroxy-6-methyl-2oxopyridin-l(2H)-yl)-4-methoxybenzoate OH 2 Me A 250 mL round bottomed flask equipped with stirbar, Dean-Stark trap and reflux condensor was charged with the product of Step 1 (23.5 g, 0.129 mol), 4-hydroxy-6-methyl-2pyrone (17.8 g, 0.14 mol), and o-dichlorobenzene (200 mL) . The system was immersed in a 170 C oil bath for 2 h and was then cooled to room temperature. The reaction mixture was washed with aqueous Na 2 CO 3 (28 g, 0.26 mol, 500 mL water). The aqueous layer was washed with ethyl acetate and then was acidified to pH 1-2 with concentrated HCI. This was extracted with ethyl acetate, which was then dried with Na 2 SO 4 and concentrated in vacuo. The viscous orange oil was triturated with MeOH to give the title compound as a yellow solid (1.61 3H) , 3.87 (s, 3H) , 1.90 (s, 3H) ppm. ES-HRMS m/z 290. 0997 (M+H calcd for C 1 sH! 6 NO requires 290.1023) . Stem 3 Preparation of methyl 3-[4-[(2,4-difiuorobenzyl)oxy]-6methy!-2-oxopyridin-l(2H)-yl]-4-methoxybenzoate F 2 Me A i00 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the product of Step 2 (1.6 g, 5.5 mmol) and N,N-dimethyl formamide (I0 mL) . 1,8- diazabicyclo[5.4.0]undec-7-ene (0.91 mL, 6 mmol) was added followed by 2,4-difluorobenzyl bromide (0.77 mL, 6 mmol) . The reaction mixture was stirred at 60 C for 4 h, was poured into saturated aqueous NaHCO and was extracted with ethyl acetate. The organic layer was washed with brine, dried with Na 2 SO 4 and concentrated in vacuo to give the title compound as an orange foam (2.13g, 93%), which was carried on to the next reaction without further purification. IH NMR (400 MHz, CD 3 OD) 6 8.17 (dd, J = 2.64 and 11.6 Hz, IH), 7.82 (td, J = 2.7 and 6.8 Hz, IH), 7.57 (m, IH), 7.29 (d, J = 11.6 Hz, IH), 7.02 (m, 2H), 6.16 (m, IH), 6.03 (d, J = 3.5 Hz, IH), 5.14 (s, 2H), 3.89 (s, 6H), 1.93 (s, 3H) ppm. 19 F NMR (400 MHz, CD OD) 6III.43(IF), -116.04 (i F) ppm. ES-HRMS m/z 416.1310 (M+H calcd for C 22 H 0 F 2 NOs requires 416.1304). Step 4 Preparation of methyl 3-[3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4methoxybenzoate A I00 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the product of Step 3 (2.1 g, 5.06 mmol) and N-methyl-2-pyrrolidine (i0 mL). N-Bromo succinimide (I g, 5.56 mmol) was added and the reaction mixture was stirred at room temperature for 1 h. The mixture poured into saturated aqueous NaHCO 3 and extracted with ethyl acetate. The organic layer was washed with brine, dried with Ma 2 SO 4, and concentrated in vacuo. The residue was chromatographed on silica (I:i hexane: ethyl acetate) to give the title compound as an orange oil (0.77 g, 31%). H NMR (400 MHz, CD 3 OD) 6 8.16 (app qd, J = 2.5 and 7.2 Hz, IH), 7.84 (d, = 2.6 Hz, IH) , 7.64 (m, IH), 7.30 (d, J = 9.2 Hz, IH), 7.04 (appt, J = 8.4 Hz, 2H), 6.60 (s, IH), 5.33 (s, 2H), 3.80 (s, 6H), 1.99 (s, 3H) ppm. 19 F NMR (400 MHz, Cb 3 OD) 6-111.56 (IF), -116.00 (I F) ppm. ES-HRMS m/z 494.0398 (M+H calcd for C 22 HIgBrF 2 NOs requires 494.0409) . Step 5 Preparation of 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]-4-methoxybenzoic acid A I00 mL round bottomed flask was charged with the product of Step 4 (0.77 g, 1.55 mmol), tetrahydrofuran (I0 mL), methanol (5 mL), and water (5 mL). To this slurry was added 2.5 N NaOH (1.2 mL, 3.1 mmol). The reaction mixture became clear after 30 minutes and the reaction was complete in 1 h by LC-MS. The organics were removed on the rotary evaporator and the remaining solution was acidified to pH 2-3 with 6N HCI. The desired compound was precipitated by the addition of water and diethyl ether and subsequent filtration. The title compound was isolated as a white powder (0.60 g, 81%). IH NMR (400 MHz, CD 3 OD) 6 8.17 (dd, J = 2.2 and 8.8 Hz, IH) , 7.82 (d, J = 2.2 Hz, IH), 7.64 (q, IH), 7.29 (d, J = 8.8 Hz, IH), 7.34 (t, J = 8.8 Hz, 2H), 6.60 (s, IH), 5.34 (s, 2H), 3.87 (s, 3H), 2.01 (s, 3H) ppm. ES-HRMS m/z 480.0259 (M+H calcd for C 21 HIvBrF 2 NOs requires 480.0253). Example 521 F Preparation of 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]-4-methoxy-N-methylbenzamide Step 1 To a reaction vessel (borosilicate culture tube) was added Example 520 (0.300 g, 0.624 mmol) and l-hydroxybenzotriazole (0.042 g, 0.31 mmol) . N,N-Dimethylformamide (3 mL) was added to the reaction vessel followed by approximately 1.06 g of the polymer bound carbodiimide resin (1.38 mmol/g) . Additional N,N-dimethylformamide (2 mL) was then added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker at approximately 200 RPM at room temperature for 15 minutes. N-Methyl amine (2 mL, 4 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with tetrahydrofuran 20 mL) and treated with approximately 2 g of polyamine resin 2.63 mmol/g) and approximately 2.5 g of methylisocyanate functionalized polystyrene (1.5 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature for 3 hours. The reaction vessel was then opened and the solution phase product was separated from the insoluble quenched byproducts by filtration and collection into a vial. After partially evaporation the insoluble byproducts were rinsed with tetrahydrofuran (2 x i0 mL) . The filtrate was evaporated by blowing N 2 over the vial and the resulting solid was triturated with diethyl ether to give the desired product as an off-white solid (0.094 g, 31%). IH NMR (400 MHz, CD]OD) 6 7.98 (dd, J = 2.2 and 8.8 Hz, IH) , 7.64 (m, 2H), 7.28 (d, J = 9.2 Hz, IH), 7.04 (t, J = 9.2 Hz, 2H), 6.60 (s, IH), 5.34 (s, 2H), 3.86 (s, 3H), 2.88 Is, 3H), 2.01 (s, 3H) ppm. 19 F NMR (400 MHz, CD OD) 6-111.59 (IF), -116.01 (I F) ppm. ES-HRMS m/z 493.0593 (M+H calcd for C 22 H 20 BrF 2 N 2 0 4 requires 493.0569). Example 522 Preparation of 3- [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6methyl -2 -oxopyridin1 (2H) -yl ] -4 -methoxy-N, Ndimethylbenzamide The title compound was prepared essentially as in Example 521. IH NMR (400 MHz, CD 3 OD) 6 7.64 (m, IH), 7.61 (dd, J = 2 and 8.8 Hz, IH), 7.33 (d, J = 2.2 Hz, IH) , 7.27 (d, J = 8 Hz, IH), 7.04 (t, J = 8 Hz, 2H), 6.59 (s, IH), 5.33 (s, 2H), 3.85 (s, 3H), 3.07 (s, 6H), 2.02 (s, 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 8 -111.60 (IF), -116.01 (I F) ppm. ES-HRMS m/z 507.0716 (M+H calcd for C 2 jH 22 BrF 2 N 2 0 4 requires 507.0726). Example 523 l-[5-(aminomethyl)-2-fluorophenyl]-3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one hydrochloride HCI Step 1 Preparation of 3-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6methyI-2-oxopyridin-l(2H)-yl]-4-fluorobenzamide A 250 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with 3- [3-chloro-4- [ (2,4difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl ] -4- fluorobenzoic acid (2.58g, 6.1 mmol), 4-methylmorpholine mL, 18.3 retool) , 2-chloro-4,6-dimethoxy-l,3,5-triazine (1.28g, 7.3 mmol) and tetrahydrofuran (30 mL). After stirring the mixture for 30 rain at 25° C, NH 4 OH (15.0 mL) was added. mixture was stirred for 30 min and diluted with water. product precipitated from solution. The precipitated was filtered and washed with water and diethyl ether to give title compound (2.55g, 78%) as a white solid. H NMR (400 (CD 3) 2 SO) 6 8.10 (m, IH) , 7.9 (dd, J = 2.1 and 5.2 Hz, IH) 7.65 (q, 6.7 and 8.5 Hz, IH), 7.56 (t, J = 9.1 Hz, IH), (td, J = 2.4 and 8.2 Hz, IH) 7.17 (td, J = 2 and 6.6 Hz, 6.78 (s, IH), 5.36 (s, 2H), 2 (s, 3H) ppm. ES-HRMS m/z 0719 (M+H calcd for C 20 HIsCIF 3 N 2 0 requires 423.0718). Step 2 Preparation of l-[5-(aminomethyl)-2-fluorophenyl]-3-chloro-4- [(2,4 difluorobenzyl)oxy]-6-methylpyridin-2(iH)~one hydrochloride A I00 mL round bottomed flask equipped with stirbar nitrogen inlet was charged with the product from step i (1.5 g, 3.5 retool), BH 3 .THF complex (7.4 mL, 7.4 retool), and tetrahydrofuran (15 mL) . The mixture was refluxed for 6 h, allowed to cool to room temperature and quenched with HCI The organics were evaporated and the remaining aqueous solution was saturated with NaOH 2.5N and extracted with dichloromethane. The organic phase was dried with Na 2 SO 4 and concentrated in vacuo. HCl 6N was added, and concentrated vacuo. IH N-MR (400 MHz, (CD 3 ) 2 SO) 6 8.2 (m, IH), 7.6 (m, IH), 7.5 (m, IH) , 7.3 (t, J = 9.8 Hz, IH) , 7.16 (t, J = 8.6 Hz, 6.78 (s, IH), 5.36 (s, 2H), 4.05 (d, J = 5.8 Hz, 2H), 2 (s, 3H) ppm. ES-HRMS m/z 409. 0940 (M+H calcd for C 20 HITCIF 3 N 2 requires 409.0925) . Example 524 3-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-4-fluoro-N-[2-hydroxy-l- (hydroxymethyl)ethyl]benzamide Preparation of 3- [3-chloro-4- [(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-I (2H) -yl] -4fluoro-N- [2-hydroxy-l- (hydroxyrnethyl) ethyl] benzamide The title compound was prepared essentially as in Example 521. IH NMR (400 MHz, CD 3 OD) 6 8.1 (m, IH), 7.8 (dd, J = 2.3 and 5.1 Hz, IH), 7.6 (q, J = 7.4 and 7.0 Hz, IH), 7.41 (t, J = 8.9 Hz, IH), 7.04 (m, 2H) 6.7 (s, IH), 5.36 (s, 2H), 4.1 (t, J = 5.8 Hz, IH), 3.7 (d, J = 5.1 Hz, 4H) 2.1 (s, 3H) ppm. ESHRMS m/z 497. 1045 (M+H calcd for C 2 H 21 CIF 3 N 2 Os requires 497.1086). Examples 525-528 The compounds of Examples 525-528 are prepared by derivitazion of Example 523. The analytica! data are shown below. JEx. No. R [ MF M+H ESHRMS [ i Requires m/z Ex. 52 5-C (O) CH 3 C 22 H 18 CI F 3 N 2 0 3 451.1 0 3 145 i. 1 0 1 0 4 8i 1136481.1132 Ex. 526-C (O) CH 2 OCH 3 C 2]H 20 CIF 3 N 2 0 4 EX. 527SO 2 CH 3 S 21 HIsCIF 3 N 2 0 4 S 487.0701487.0679 Ex. 528-C (O) NH 2:C 21 HI 6 CIF 3 N 3 0 3 452.0983452.0987 NMR characterization of compounds of Examples 525-528 Ex. No. NMR Data 525 IH NMR (400 M]4z, CODED) 6 7.6 (q, J = 7.8 and 7.0 Hz, iH), 7.3 (t, J = 9.0 Hz, IH), 7.2 (dd, J = 1.9 and 5.1 7.05 (m, 2H}, 6.65 (s, IH}, 5.36 (s, 2H), 4.39 (s, 2H), 3H) , 1.98 (s, 3H) ppm 526 IH NMR (400 MHz, CD CI ) 6 7.45 (q, J = 8.6 and 6.2 Hz, (m, IH), 7.1 (m, 2H), 6.85 (q, J = 6.5 and 1.9 Hz, IH), J = 2.7 and ?.8 Hz, IH), 6.2 (s, IH), 5.2 (s, 2H), 4.39 6.2 Hz, 2H), 4.0 (s, 3H) 2.3 (s, 2H), 2.0 (s, 3H}, I 98 ppm 527 IH NMR (400 MHZ, CODED) 6 7.49 (q, J = 8.2 and 6.3 Hz, (m, IH) , 7.23(m, iH), 7.1 (t, J = 8.9, IH), 6.9 (td, J 6.6 IH), 6.8 (td, J = 2.7 and 6.25 Hz, IH), 6.2 (s, IH) 2H), 4.2 (s, 2H), 2.8 (s, 3H) 2.0 (s, 3H) ppm 528 IH KTMR (400 MHz, (CD ) 2 SO) 6 7.61 (q, J = 8.9 and 6.6 Hz, 7.38(d, J = 9.8 Hz, IH), 7.3 (d, J = 10.2 Hz, IH) 7.21 Hz, IH) , 7.1 (t, J = 8.6 HZ, IH), 6.71 (s, IH) , 6.5 (t, Hz, IH), 5.56 Is, 2H), 5.3 Is, 2H), 4.]8 Id, O = 6.25 3.61 (s, IH), 1.98 (s, 3H) ppm Example 529 2- ({ [3-chloro-l-(2,6-difluorophenyl)-6-methyl-2-oxo-l,2dihydropyridin-4-yl]oxy}methyl)-5-fluorobenzonitrile 2- (bromomethyl)-5-fluorobenzonitrile (3.47 g, 16.2 mmol), 3chloro-l-(2,6-difluorophenyl)-4-hydroxy-6-methylpyridin-2(iH)- one (3.15 g, 11.6 mmol), K 2 C0 3 (2.56 g, 18.6 mmol), and 18crown-6 (0.15 g) were dissolved in N,N-dimethylacetamide (25 mL) . Reaction mixture stirred on 60°C oil bath for 4 hours. Solvent removed by distillation. Reaction neutralized with 5% citric acid. The solid product was washed with hexane followed by 30% EtOAc/hexane. Filtered a brown solid (5.2 g, 79% yield). IH N R (CD OD / 400MHz) 67.82 (m, 2H), 7.61 (m, 4H), 6.75 (s, IH), 5.49 (s, 2H), 2.13 (s, 3H) . ESHRMS m/z 405.0616 (M+H C 20 HIHCIF 3 N 2 0 2 requires 405.0612). Example 530 4- { [2- (aminomethyl) -4-fluorobenzyl] oxy} -3-chloro-l- (2,6difluorophenyl)-6-methylpyridin-2(iH)-one trifluoroacetate BH 3 THF (17.8 mL, 17.8 mmol) was added dropwise to a chilled (0°C) solution of 2-({[3-chloro-l-(2,6-difluorophenyl)- 6-methyl-2-oxo-l,2-dihydropyridin-4-yl]oxy}methyl)-5fluorobenzonitrile (3.61 g, 8.92 mmol) in THF (30 mL) . Following the addition, the reaction was heated at 60°C for 1.5 hours. The reaction was quenched with MeOH, the solvent evaporated, and the crude product purified by prep HPLC. The product was isolated by freeze-drying and evaporation of the solvent to give a white solid (1.52 g, 32.6%). IH NMR (CD 3 OD/ 2.14 (s, 3H) . ESHRMS m/z 409.0900 (M+H C 0 HI N=OcF 3 CI requires 409.0925). Examples 531-551 NH R The compounds of Examples 531-551 are prepared by derivitazion of Example 530. The analytical data are shown below. ompound M+H ESHRMS NO. R MF Requires m/z x. 531-OCH 3 1 22 HI 8 CI F 3 N 2 0 4 467.0980 467.0985 Ex. 532-CF 3 C 22 HIsCI F 6 NaO 3 505.0748 505.0754 Ex. 533-O-isopropyl C 24 HnCIFaN O 4 95.1293 495.1304 480. 129 6 Ex. 534-NH-CH 2 CH 3 S 23 H 21 CIFHN O 3 480.1277 Ex. 535-Otetrahydrofuran3-yl C 2 sH 22 CI FHN 2 0s 523.1242 523.1282 iEx. 536 -O-propyl C 24 H 22 CIF 3 N 2 0 4 495.1293 495.1338 Ex. 537-O-CH 2 CH=CH 2 C 24 H 20 CIFHN 2 0 4 493.1136 493.1116 Ex. 538-O-CH 2 CmCH C 24 HIsCIF 3 N 2 0 4 491.0980 491.0961 Ex. 53 9 -O-tButyl C 2 sH 24 CIF 3 N 2 0 4 509.1449 509.1436 Ex. 540-N-H-tButyl C 2 sH 2 sCI F 3 N]O] 508.1609 508. 1574 54 2 - SOHCH 2 CH 543-NHisopropyl S 24 H= 3 CIF 3 N]O 494.1453 94.1456 544CH 2 OCH 3 IC 23 H 20 Ci F 3 N 2 0 4 481.1136481.1174 5 4 5NHCH 3 S 22 H' 20 CIFHN]O 3 466.1140466.1141 546-N (CH 3 )(tButy!) C 26 H 2 vCIF 3 N]O] 522.1766522.1737 547-NTH (cyc lopropyl ) C 24 H 21 CIFHN 303 492.1296492.1285 548-NHCH 2 CF 3 C 23 HzTCIF 6 N 30 534.1014534.1005 549 N-HCH 2 (cyclopropyl) C 2 sH aCl F 3 N 3 0 506.1453506.1432 550NHCH 2 ( tButyl ) C 26 H 2 vCIF 3 N 3 0 3 522.1766522.1740 551-N (CH 3 ) 2 C 23 HH 2 CIF 3 N 3 0 3 480.1296480.1307 characterization of compounds of Examples No. NMR data NNMR J = 2H), = 5.2 NNMR J = 2H) NNMR J 2H), 4.47 (s, 2H), 2.70 (s, 3H), 2.14 (s, 3H). ESHRMS m/z 466.1141 (M+H C 2 H 20 CIFHN 3 0] requires 466. 1140) . Example 552 O 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-{ [5-(l-hydroxy-lmethylethyl)pyridin-2-yl]methyl}-6-methylpyridin-2(IH)-one Step I: Preparation of methyl 6-methylnicotinate 1-oxide O O Methyl 6-methylnicotinate (6.0 g, 39.7 mmol) was added into dichloromethane (i00 mL) in the round bottom flask under nitrogen. 3-chloroperoxybenzoic acid (I0.0 g, 57.9 mmol) was then added into the flask and stirred for 5 hour. Saturated sodium bicarbonate solution (i00 ml) was added into the reaction and the mixture was transferred to separatory funnel. Additional 200mL of dichloromethane was added into the funnel and obtained the organic layer. The organic layer was washed with water (150 mL) and dried over anhydrous magnesium sulfate. The resulting solution was evaporated to yield white solid (6 g, 90 %). LC/MS, tr = 0.33 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 168 (M+H) . ES-HRMS m/z 168.0628 (M+H calcd for CeH 10 N0 3 requires 168.0655). Step 2: Preparation of methyl 6-(chloromethyl)nicotinate O Ck Methyl 6-methylnicotinate 1-oxide ( from Step i) (6.0 g, 35.9 mmol) was was added into the p-toluenesulfonyl chloride (I0 g, 52.4 mmol) in i00 mL of 1,4dioxane. The mixture was heated to reflux for 20 hours. Saturated sodium bicarbonate solution (200 ml) was added into the reaction and the mixture was transferred to separatory funnel. The compound was extracted using ethyl acetate 1300ml x 2) and the combined ethyl acetate solution was dried over magnesium sulfate and evaporated to black solid (5.2 g, 78%). LC/MS, tr = 1.52 minutes [5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 186 (M+H) . ES-HRMS m/z 186.0314 (M+H calcd for CsHgCINO 2 requires 186.0316). Step 3: Preparation of methyl 6-{ [4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}nicotinate Methyl 6-(chloromethyl)nicotinate ( from step 2). (2 g, 10.8 mmol) was added into 4-[(2,4-difluorobenzyl)oxy]-6methylpyridin-2(IH)-one in 20 mL of dimethyl formamide followed by addition of cesium carbonate (59, 15.3 mmol). The mixture was heated to i00 C for 20 hours. It was cooled to room temperature and added 400 mL of water. Brown precipitate came out of from solution. It was filtered and rinsed with water (200 mL x 3) and dried to obtain 4 g of solid. The product was purified using a Wilson Reversed Phase preparative chromatography to obtain white solid (1.4 g, 32%). IH NMR (400 MHz, CDCI ) 6 9.09 (d, J =1.48 Hz, IH) , 8.19 (dd, J = 6.04, 2.15 Hz, IH), 7.37 (app q, J = 8.32 Hz, IH), 7.25 (d, J = 8.33 Hz, IH) , 6.84 (m, 2H) , 5.94 (d, J = 2.82Hz, IH) , 5.83 (d, J = 2.15Hz, IH) , 5.36 (s, 2H) , 4.97 (s, 2H) , 3.90 (s, 3H) , 2.27 (s, 3H) ; LC/MS, tr = 2.30 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 401 (M+H) . ES-HRMS m/z 401.1307 (M+H calcd for C 21 HIgF 2 N 2 0 4 requires 401.1307) . Step 4: Preparation of the title compound . 3 molar solution of methyl magnesium bromide in ether (5mL, 15mmol) was added into 5 ml of anhydrous tetrahydrofuran in the round bottom flaks under nitrogen. The mixture was cooled to 0°C. Methyl 6-([4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}nicotinate ( from Step 3) (300mg, 0.75mmol)was dissolved in 5 ml of anhydrous tetrahydrofuran in dropper funnel and the solution was slowly added into cold methyl magnesium bromide solution in the round bottom flask. After the addition, the mixture was continue stirring at 0 C for 30 minute and cold solution of saturated ammonium chloride (i00 ml) was added slowly into the reaction mixture. The mixture was transferred to separatory funne! and the product was extracted with ethyl acetate (200ml x2). The combined ethyl acetate solution was dried over anhydrous magnesium sulfate and evaporated to dryness. The resulting residue (220 mg) was added into I0 ml of dichloromethane followed by addition of N-bromo succinimide (i00 mg, 0.56 mmol) . The solution was stirred at room temperature for 3 hours. Saturated sodium bicarbonate solution (i00 ml) was added into the reaction mixture and it was transferred to separatory funnel. The product was extracted with ethyl acetate (200ml x2). The combined ethyl acetate solution was dried over anhydrous magnesium sulfate and evaporated to dryness. H NMR (400 MHz, CDCI 3 ) 5 8.61 (d, J =1.88 Hz, IH), 7.73 (dd, = 5.77, 2.42 Hz, IH), 7.55 (app q, J = 6.31 Hz, IH), 7.30 (d, J = 8.19b Hz, IH) , 6.93 (m, IH) , 6.84 (m, IH) , 6.00 (s, IH) , 5.37 (s, 2H) , 5.19 (s, 2H) , 2.48 (s, 3H) , 1.56 (s, 6H) ; LC/MS, tr = 2.29 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 479 (M+H) . ES-HRMS m/z 479.0791 (M+H calcd for C 2 H 22 BrF 2 N 2 0 requires 479.0776). Example 553 N oH Br <N 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -i- { [5- (hydroxymet hyl ) pyridin2 -yl ] methyl } - 6 -met hylpyridin2 (IH) -one Step i: Preparation of 4- [(2,4-difluorobenzyl)oxy]-l-{ [5- (hydroxymethyl) pyridin2 -yl] methyl } -6-methylpyridin-2 (IH) -one Methyl 6-{[4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}nicotinate ( from preparation of step 3) (350 mg, 0.87 mmol) was added into anhydrous tetrahydrofuran (15 ml) and the solution was cooled to -78 C. Into the cold solution, was added lithium aluminum hydride (i00 mg, 2.6 mmol). After the addition, the reaction mixture was warm to 0 C and continue stirring for one additional hour. Potassium hydrogen sulfate (i N solution, 150 ml) was added slowly into the reaction mixture to quench the reaction. The resulting mixture was transferred to a separatory funnel and the product was extracted with ethyl acetate (200ml x 2). The combine ethyl acetate solution was dried over anhydrous magnesium sulfate and evaporated to dryness. LC/MS, tr = 1.88 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 373 (M+H) Step 2: Preparation of the title compound 4-[(2,4-difluorobenzyl)oxy]-l-{[5-(hydroxymethyl)pyridin-2yl]methyl}-6-methylpyridin-2(IH)-one ( from step I). (230 mg, 0.62 mmol) was added into i0 ml of dichloromethane followed by addition of N-bromo succinimide (ii0 mg, 0.62 mmol). The solution was stirred at room temperature for 3 hours. Saturated sodium bicarbonate solution (i00 ml) was added into the reaction mixture and it was transferred to a separatory funnel. The product was extracted with ethyl acetate (200ml x2) . The combined ethyl acetate solution was dried over anhydrous magnesium sulfate and evaporated to dryness. IH N-MR minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 451 (M+H) Example 554 O 6- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl] methyl } -N- (2-hydroxyethyl) -N-methylnicotinamide Step i: Preparation of methyl 6-{[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}nicotinate F F 0 o N JJ..o/ Methyl 6-{[4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}nicotinate (350 mg, 0.87 mmol) (i.0 g, 2.5 mmol) was added into 150 ml of dichloromethane followed by addition of N-bromo succinimide (500 mg, 2.8 mmol). The solution was stirred at room temperature for 3 hours. Saturated sodium bicarbonate solution (300 ml) was added into the reaction mixture and it was transferred to a separatory funnel. The product was extracted with ethyl acetate (500ml x2) . The combined ethyl acetate solution was dried over anhydrous magnesium sulfate and evaporated to dryness. H NMR 2.85 minutes (5 to 95% acetonitrileiwater over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 479 (M+H) . ESHRMS m/z 479. 0415 (M+H calcd for CnHIsBrF 2 N 2 0 4 requires 479.0413) . Step 2: Preparation of 6-{[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}nicotinic acid O Methyl 6-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl- 2-oxopyridin-l(2H)- ylJmethyl}nicotinate ( from step i) (i.0 g, 2.1 mmol) was added into the mixture of i00 ml tetrahydrofuran and I0 ml of methanol followed by addition of 2.5 N sodium hydroxide(0.85 ml, 2.1 mmol). The solution was heated to 50 C for 2 hours. After the solution was cooled to room temperature and evaporate to completely dried residue. The residue was added into 50 ml of tetrahydrofuran and 4 N HCI in 1,4-dioxane (0.52 ml, 2.1 mmol) and stirred the mixture for 30 minute. The mixture was evaporate to dryness. The residue was added 20 ml water and the aqueous solution was neutralized to exactly ph 7 by addition of saturated sodium bicarbonate solution drop wise. The resulting heterogeneous mixture was left standed for 20 hours. Filtered, rinsed with water (30 ml x 3) and dried over high vacuum oven to afford white solid( 950 mg, 97%). 2.48 minutes (5 to 95% acetonitri!e/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 465 (M+H) . ES-HRMS m/z 465.0254 (M+H calcd for C 20 HI BrF N 2 0 4 requires 465.0256). Step 3: Preparation of the title compound 6- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin-I (2H)-yl]methyl}nicotinic acid ( from step 2) (230 mg, 0.5 mmol) was added into the l-hydroxybenzotriazole (101mg, 0.75 mmol) in 5 ml of N,N-dimethylforamide. 4 -methyl morpholine (0.16 ml, 1.5 mmol) was added into the mixture followed by addition of l-(3-(dimethylamino) propyl-3ethylcarbodiimide hydrochloride (143 mg, 0.75 mmol). Stirred the mixture for 30 minute to become homogenous solution. To that homogenous solution, was added 2-(methylamino) ethanol(0.06 ml, 0.75 mmol) and the mixture was stirred for hours. Water (150 ml) was added into the reaction mixture and the product was extracted using ethyl acetate (400ml x2). The combined ethyl acetate solution was dried over anhydrous magnesium sulfate and evaporated to dryness. IH NMR (400 MHz, DMSO-dG) 6 8.47 (app br s, IH), 7.80 (br d, J = 7.92 Hz, IH), 7.64 (app q, J = 6.58 Hz, IH), 7.30 (m, 2H), 7.15 (m, IH), 6.56 (s, IH), 5.39 (s, 2H), 5.28 (s, 2H), 3.46 (m, 2H), 3.23 (m, 2H) 2.93 (m, 3H), 2.36 (s, 3H) ; LC/MS, tr = 2.29 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-HRMS m/z 522.0850 (M+H calcd for C 23 H 3 BrF 2 N 3 0 4 requires 522.0835). Example 555 6-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]methyl}-N- (2-hydroxyethyl)nicotinamide Following the method of Example 554 (step 3) and substituting 2-(methylamino)ethanol for the ethanolamine obtained the title compound as a white solid (79% yield). IH NMR (400 MHz, CD 3 OD) 6 8.93 (d, J = 2.01 Hz, IH), 8.21 (dd 0 J = 6.04, 2.21 Hz, !H) , 7.67 (app q, J = 6.44 Hz, IH), 7.39 (d, J = 8.06 Hz, IH), 7.08 (m, 2H), 6.58 (s, IH), 5.55 (s, 2H), 5.35 (s, 2H), 3.74 (app t, J = 5.73Hz, 2H), 3.53 (app t, J = 5.73Hz, 2H), 2.49 (s, 3H) ; LC/MS, tr = 2.26 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-HRMS m/z 508.0673 (M+H calcd for CnH 21 BrF 2 N 3 0 4 requires 508.0678). Example 556 6- { [3-bromo-4- [ (2,4 -dif luorobenzyl) oxy] -6-methyl2-oxopyridin1 (2H) -yl] methyl } -N, N-dimethylnicotinamide Following the method of Example 554 (step 3) and substituting dimethylamine for the ethanolamine obtained the title compound as a white solid (75% yield). IH NMR (400 MHz, CDCI 3 ) 6 8.55 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 m!/min with detection 254 nm, at 50°C). ES-HRMS m/z 492.0710 (M+H calcd for C 22 H 21 BrF 2 N 3 0 3 requires 492.0729). Example 557 O 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-[2- (trifluoromethyl)phenyl]pyridin-2(IH)-one Step i: Preparation of 4-hydroxyl-6-methyl-l- [2trifluoromethyl)phenyl]pyridin-2(iH)-one HO"-fiw CF 3 4-hydroxy-6-methyl-2-pyrone (10g, 79.3 mmol) was added into the 2-(trifluoromethyl) aniline (14 ml, 111.3 mmol) in I0 ml of 1,2-dichlorobenzene in a round bottom flask. The mixture was then placed in a pre-heated oil bath at 165 C. After 30 minute of heating, the mixture was cooled to room temperature and added 250 ml of saturated sodium bicarbonate solution. The mixture was stirred at room temperature for minutes and transferred to a separator funnel. Ethyl acetate (300ml) was added into the separatory funnel and partitions the layers. The aqueous layer was obtained and the organic layer was added 200 ml of saturated sodium bicarbonate solution. The aqueous layer was obtained again and the combined aqueous solution was neutralized with HCI solution. Upon neutralization, white solid precipitated out of the solution. Filtered the solid, rinsed with water (I00 ml x5) and dried over high vacuum oven to obtain the white solid (7.5 g, 35.5%). LC/MS, tr = 1.77 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 270 (M+H) . Step 2: Preparation of 4- [(2,4-difluorobenzyl)oxy]-6-methyll-[2-(trifluoromethyl)phenyl]pyridin-2(iH)-one 4-hydroxy-6-methyl-l-[2-(trifluoromethyl)phenyl]pyridin-2(iH)- one ( from Step i) (7.3 g, 27.1 mmol) was added into 3,4difluorobenzyl bromide (5.5 g, 26.5 mmol) in 60 ml of dimethyl formamide. The mixture was cooled to 0 C and cesium carbonate (20g, 61.3 mmol) was added into the mixture. After the addition, the mixture was warmed to room temperature and stirred for 4 hours. Water (500ml) was added into the reaction mixture. Yellow solid came out of solution. Filtered and rinsed with water (200ml x 2) to obtain the yellow solid. Dissolved the solid in ethyl acetate (500 ml) and water (300 ml) and transfer to a separatory funnel and obtained the organic layer. The organic layer was washed again with water (200ml) and dried over anhydrous magnesium sulfate. The organic solution was evaporated to dryness. IH 2.94 Hz, 2H), 1.86 (s, 3H); LC/MS, tr = 2.74 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 396 (M+H) Step 3: Preparation of the title compound. N-bromosuccinimide (0.24g, 1.36 mmol) was added into 4-[(2,4difluorobenzyl)oxy]-6-methyl-l-[2- (trifluoromethyl)phenylJpyridin-2(iH)-one (0.54g, 1.36 mmol) in 20 ml of dichloromethane. The mixture was stirred at room temperature for 2 hours. Saturated sodium bicarbonate solution (150 ml) was added into the reaction mixture and the combine solution was transferred to a separatory funnel. The product was extracted with ethyl acetate (250mi). The ethyl acetate solution was dried over anhydrous magnesium sulfate and evaporated to dryness. IH NMR (400 MHz, CDCI 3 ) 6 7.82 (d, J =7.25 Hz, IH), 7.7 (app t, J = 7.66 Hz, IH), 7.60 (m, 2H), 7.26 (s, IH) , 6.97 (m, IH), 6.87 (m, IH) , 6.09 (s, IH) , 5.25 (app d, J = 3.35Hz, 2H), 1.94 (s, 3H) ; LC/MS, tr = 2.84 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-HRMS m/z 474.0113 (M+H calcd for C 20 HI 4 BrFsNOa requires 474.0123). Example 558 F F 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-6methyl-5-vinylpyridin-2 (IH) -one Step i: To a room temperature solution of 3-bromo-4- [(2,4 difluorobenzyl) oxy] - i- (2,6-difluorophenyl) -5-iodo-6methylpyridin-2(iH)-one (i.00 g, 1.76 mmol) in anhydrous THF (12 mL) was added, sequentially, tributyl (vinyl) tin (1.21 g, 3.81 retool) and tetrakis (triphenylphosphine)palladium (236 rag, 0.204 mmol) under an argon stream. The reaction vessel was then equipped with a reflux condenser and the reaction system purged with an argon flow. The resulting yellow solution was heated to 68 °C and stirred under a positive pressure of argon for 12.0 hours until complete disappearance of starting material by LCMS analysis. The reaction mixture was concentrated in vacuo and the resulting dark residue was subjected to SiO 2 chromatography with ethyl acetate/hexanes (3:7) to furnish a reddish solid, iH N-MR (400 MHz, CDCI 3 ) 6 7.62 (app q, J = 7.8 Hz, IH), 7.45 (app tt, J = 8.4, 6.2, IH), 7.09 (app t, J = 8.8 Hz, 2H) , 6.90 (app t, J = 8.0 Hz, IH) , 6.83 (app dt, J = 6.8, 2.5 Hz, IH) , 6.51 (dd, J = 17.7, 11.4 Hz, IH), 5.53 (dd, J = 11.4, 1.5 Hz, IH), 5.41 (dd, J = 17.8, 1.5 Hz, IH) , 5.09 (br s, 2H) , 2.09 (s, 3H) ; LC/MS C-18 column, tr = 3.20 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 468 (M+H). ES-HRMS m/z 468.0210 (M+H calcd for C 21 HIsBrF 4 N0 2 requires 468.0217} . Example 560 (l,2-dihydroxyethyl)-6-methylpyridin-2(IH)-one Step I: To a room temperature solution of 3-bromo-4- [(2,4- difluorobenzyl)oxy]-l-(2,5-difluorophenyl)-6-methyl-5vinylpyridin-2(IH)-one (0.970 g, 2.07 mmol) in water/acetone 1:3 (8.7 mL) was added, sequentially, osmium tetroxide (0.ii0 g, 0.433 mmol) and N-methyl morpholine oxide (1.32 g, 11.2 mmol) . The resulting solution was stirred for one hour until complete consumption of starting material by LCMS analysis, and the reaction was concentrated in vacuo. The resulting dark residue was subjected to SiO 2 chromatography with ethyl acetate/hexanes (3:7) to furnish a solid. IH NMR (400 MHz, CDCI 3) 6 7.59 (app q, J = 8.2 Hz, IH), 7.45 (ddd, J = 14.7, 8.5, 6.8 Hz, IH), 7.08 (app t, J = 8.5 Hz, 2H), 6.94 (app t, J = 8.2 Hz, IH), 6.88 (app t, J = 8.5 Hz, IH), 5.31 (AB-q 0 J = 10.6 Hz, A= 38.3 Hz, 2H), 5.07 (dd, J = 9.1, 3.8 Hz, IH), 3.83 (t, J = 10.8 Hz, IH), 3.60 (dd, J = 11.4, 3.9 Hz, IH), 2.94 (br s, IH), 2.16 (s, 3H) ; LC/MS C-18 column, tr = 2.26 minutes (5 to 95% acetonitrile/water over 5 minutes at i ml/min with detection 254 nm, at 50°C). ES-MS m/z 502 (M+H). ES-HRMS m/z 502.0276 (M+H calcd for C 21 HITBrF 4 NO 4 requires 502.0272). Example 561 F 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-5- (hydroxymethyl)-6-methylpyridin-2(iH)-one Step I: To a -20 °C solution of 5-bromo-4- [ (2,4difluorobenzyl)oxy]-l- (2,6-difluorophenyl)-2-methyI-6-oxo-l,6dihydrop],ridine3 - carbal dehyde (0.659 g, ! .40 mmol) in methanol (i0 mL) was added, port ionwise, solid sodium borohyride (3.6 g, 96 mmol) over one hour until complete consumption of starting material by LCMS analysis. Next, the reaction mixture was diluted with 500 mL of ethyl acetate and washed with 3 X 200 mL of water. The resulting organic extract was Na 2 S0 4 dried, filtered, and concentrated in vacuo to approximately i00 mL volume. The resulting liquid was diluted with hexanes (i00 mL) to furnish an amorphous solid that was collected and dried at 1 mm Hg vacuum to furnish (620 mg, 94 %) of the desired product. IH NMR (400 MHz, d 4 -MeOH) 6 7.70 (app q, J = 8.3 Hz, IHI, 7.62 (app tt, J = 10.4, 6.3 Hz, IH), 7.25 (app t, J = 8.6 Hz, 2H}, 7.03 (app t, J = 8.6 Hz, IH} , 6.88 (app t, J = 8.5 Hz, !H), 5.31 (s, 2H), 4.58 (s, 2H), 2.17 (s, 3H) ; LC/MS C-18 column, tr = 2.49 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 472 (M+H) . ES-HRMS m/z 472.0152 (M+H calcd for C 20 HIsBrF 4 NO 3 requires 472.0166). Example 562 4-(benzyloxy)-3-bromo-l-(2,6-difluorophenyl)-6-methylpyridin- 2(iH)-one Step I: Preparation of 4-(benzyloxy)-l- (2,6-difluorophenyl)- 6-methylpyridin-2(iH)-one To a briskly stirred room temperature solution of l-(2,6difluorophenyl)-4-hydroxy-6-methylpyridin-2(IH)-one (1.43 g, 6.03 mmol) in dimethylformamide (4.6 mL) was added sequentially K C0 3 (2.01 g, 14.5 mmol) and benzyl bromide (2.40 LL, 20.2 mmol) . The resulting suspension was stirred for 6.5 hours until complete consumption of starting material by LCMS analysis. The reaction was then diluted with ethyl acetate (200 mL) and brine washed (3 X 200 mL). The resulting organic extract was Na 2 SO 4 dried, filtered, and concentrated in vacuo to approximately I00 mL volume. The resulting mother liquor rapidly precipitated and furnished an amorphous solid that was collected and dried at 1 mm Hg vacuum to provide a solid (1.62 g, 82 %). iH NMR (300 MHz, d 4 -MeOH) 6 7.62 (app tt, J = 8.6, 6.4 Hz, IH) , 7.52-7.32 (m, 4H) , 7.30-7.12 (m, 3H), 6.27 (d, J = 1.6 Hz, IH), 6.04 (d, J = 2.6 Hz, IH), 5.18 (S, 2H), 2.06 (s, 3H). LC/MS C-18 column, t r = 2.51 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 328 (M+H). ES-HRMS m/z 328.1179 (M+H calcd for C gH: 6 F 2 N0 2 requires 328.1144). Step 2: To a room temperature solution of 4-(benzyloxy)-l- (2,6-difluorophenyl)-6-methylpyridin-2(IH)-one (1.52 g, 4.64 mmol) in methylene chloride (15 mL) was added solid Nbromosuccinimide (2.01 g, 11.3 mmol) and the resulting reddish solution was stirred for 4.0 hours. At this time the reaction was diluted with ethyl acetate (400 mL) and washed with sodium sulfite (5 % aqueous solution, i00 mL) and brine (3 X 200 mL) . The resulting organic extracts were Na 2 SO dried, filtered, and concentrated in vacuo to approximately 60 mL volume. The resulting mother liquolrapidly precipitated and furnished an amorphous solid that was collected and dried at 1 mm Hg vacuum to provide a solid (1.70 g, 91%). H N-MR (300 MHz, d 4 -MeOH) 7.64 app tt, J-- 8.6, 6.4 Hz, IH), 7.57 {br d, J = 7.1 Hz, IH), 7.50-7.34 {m, 4H), 7.27 (app t, J = 8.0 Hz, IH), 7.26-7.21 (m, IH), 6.66 (s, IH), 5.40 (s, 2H), 2.12 (s, 3H) ; LC/MS C-18 column, tr = 2.63 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 406 (M+H) . ES-HRMS m/z 406.0228 (M+H calcd for C 19 HIsBrF 2 NO 2 requires 406.0249). Example 563 F F 5-bromo-4-[(2,4-difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-2methyl-6-oxo-l,6-dihydropyridin-3-yl]methyl carbamate Step I: To a room temperature solution of 3-bromo-4-[(2,4- difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-5-(hydroxymethyl)- 6-methylpyridin-2(IH)-one (76.2 mg, 0.161mmol) in methylene chloride (0.4 mL) was added a solution of trichloroacetyl isocyanate (toluene, 0.60 M, 0.5 mL, 0.30 mmol). The resulting solution was stirred for one hour until complete consumption of starting material by LCMS analysis. The reaction mixture was then directly applied to AI 2 0s (0.5 g of Broeckman-activity type I) and the slurry was matured for three hours. At this time, the AI 2 0 plug was flushed with ethyl acetate/methanol (95:5) and the resulting mother liquor was concentrated to a residue that was subjected to SiO chromatography using ethyl acetate/hexanes (i:I) to furnish a white solid (71.0 mg, %). IH NMR (400 MHz, d 4 -MeOH) 6 7.71-7.59 (m, 2H), 7.26 (app t, J = 8.5 Hz, 2H), 7.02 (app t, J = 9.2 Hz, 2H), 5.32 (s, 2H), 5.02 (s, 2H) , 2.15 (s, 3H) ; LC/MS C~18 column, tr = 2.35 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 515 (M+H) . ES-HRMS m/z 515. 0188 (M+H calcd for C= HI 6 BrF 4 N 2 0 4 requires 515.0224) . Example 564 5-bromo-4-[(2,4-difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-2methyl-6-oxo-l,6-dihydropyridine-3-carbaldehyde Step l: To a room temperature solution of 3-bromo-4-[(2,4difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-5-(1,2dihydroxyethyl)- 6-methylpyridin-2(iH)-one (550 mg, i.i0 mmol) in toluene (I0.0 mL) was added lead(IV) acetate (810 mg, 1.82 mmol). The resulting dark brown solution was stirred for two hours until complete consumption of starting material by LCMS analysis. The reaction mixture was then diluted with ethyl acetate (400 mL), water washed (3 X i00 mL), and brine washed (3 X 300 mL) . The resulting organic extract was separated, Na 2 SO 4 dried, and concentrated. The resulting dark residue was subjected to SiO 2 chromatography with ethyl acetate/ hexanes (i:i) to furnish a light yellow solid (321 rag, 62 %). H NMR (400 MHz, CDCI 3 ) 6 10.08 (s, IH), 7.56-7.48 (m, 2H), 7.12 (app t, J = 7.3 Hz, 2H), 6.94 (app t, J = 8.5 Hz, IH), 6.88 (app t, J = 8.7 Hz, IH), 5.33 (s, 2H), 2.45 (s, 3H) ; LC/MS C-18 column, tr = 2.94 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 470 (M+H) . ES-HRMS m/z 469.9996 (M+H calcd for C 20 HI 3 BrF 4 NO 3 requires 470.0009). Example 565 F 5-bromo-4-[(2,4-difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-2methyl-6-oxo-l,6-dihydropyridine-3-carbaldehyde oxime Step I: To a room temperature solution of 5-bromo-4-[(2,4difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-2-methyI-6-oxo-l,6dihydropyridine-3-carbaldehyde (316.5 mg, 0.673 mmol) in methanol (i0.0 mL) was added solid NH 2 OH.H 2 0(300.0 mg, 4.32 mmol) and sodium acetate (480.0 mg, 5.85 mmol). The resulting suspension was stirred for 1.5 hours until complete consumption of starting material by LCMS analysis. The reaction mixture was then concentrated in vacuo and the resulting residue was diluted with methylene chloride (300 mL) and water washed (2 X I00 mL). The resulting organic extract was separated, Na 2 SO 4 dried, and concentrated to furnish a LC/MS C-18 column, tr = 2.61 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 485 (M+H). ES-HRMS m/z 485.0093 (M+H calcd for C 20 HI 4 BrF 4 N O 3 requires 485.0118). Example 566 O F 5-bromo-4-[(2,4-difluorobenzyl)oxy]-l~(2,6-difluorophenyl)-2methyl-6-oxo-l,6-dihydropyridine-3-carbonitrile Step i: To a room temperature solution of 5-bromo-4-[(2,4difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-2-methyl-6-oxo-l,6dihydropyridine-3-carbaldehyde oxime (340.0 mg, 0.701mmol) in methylene chloride (8.0 mL) was added solid i,i' carbonyl diimidazole (290.0 mg, 1.79 mmol) and sodium acetate (480.0 mg, 5.85 mmol). The resulting solution was stirred for 1.5 hours until complete consumption of starting material by LCMS analysis. The reaction mixture was then concentrated in vacuo and the resulting residue was directly applied to SiO 2 chromatography with ethyl acetate/hexanes (3:7) to furnish a white solid (262 mg, 90 %). IH NMR (400 MHz, CDCI 3 ) 8 7.61 2.32 (s, 3H) ; LC/MS C-18 column, tr = 2.95 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . IR (neat) 3111, 3067, 3032, 2914, 2840, 2215 (nitrile stretch), 1678, 1587, 1470 cm-i; ES-MS m/z 467 (M+H) . ES-HRMS m/z 467. 0037 (M+H calcd for C 20 HI 2 BrF 4 N 2 0 2 requires 467.0013). Example 567 4-(benzyloxy)-3-bromo-l-(2,6-difluorophenyl)-5-iodo-6methylpyridin-2 (IH) -one Step i: A solution of 4-(benzyloxy)-3-bromo-l-(2,6difluorophenyl)-6-methylpyridin-2(iH)-one (1.42 g, 3.50 mmol) in 1,2 dichloroethane (18 mL) was treated with solid Niodosuccinimide (1.59 g, 7.06 mmol) and dichloroacetic acid (0.260 g, 2.01 mmol). The resulting solution was stirred and heated to 50 °C for 2.5 hours until complete consumption of starting material by LCMS. At this time the reaction was diluted with ethyl acetate (400 mL) and washed with sodium sulfite (5 % aqueous solution, i00 mL) and brine (3 X 200 mL). The resulting organic extracts were Na 2 SO 4 dried, filtered, and concentrated in vacuo to approximately 30 mL volume. The resulting mother liquor rapidly precipitated and furnished an amorphous solid that was collected and dried at 1 mm Hg vacuum to provide a solid (1.49 g, 82 %). IH NMR (400 MHz, CDCI 3 ) 6 7.62 (app d, J = 6.8 Hz, 2H), 7.51-7.38 (m, 4H), 7.09 (app t, J = 8.0 Hz, 2H), 5.20 (s, 2H), 2.39 (s, 3H) ; LC/MS C-18 column, tr = 3.28 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 532 [M+H) . ES-HRMS m/z 531.9196 (M+H calcd for C=gHI BrF 2 1NO 2 requires 531.9215). Example 568 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-(2,6-dif!uorophenyl)-6methyl-5-oxiran-2-ylpyridin-2(iH)-one Step i: A sample of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l- (2,6-difluorophenyl)-6-methyl-5-vinylpyridin-2(IH)-one (i0.0 mg, 0.0214 mmol) was treated with a solution of dimethyl dioxirane in acetone (approx. 0.i M, 5 mL, 0.5 mmol). The reaction vessel was capped and sealed, and the resulting solution was stirred 6.0 hours. At this time the reaction was concentrated in vacuo and the resulting residue was subjected to SiO 2 chromatography with ethyl acetate/hexanes (4:6) to furnish a semi-solid (5.0 mg, 48 %). IH NMR (400 MHz, CDCI ) 6 7.57 (app q, J = 7.4 Hz, IH), 7.46 (app tt, J = 8.5, 6.2, IH), 7.11 (app t, J = 8.0 Hz, 2H), 6.94(app t, J = 8.2 Hz, IH), 6.83 (app t, J = 9.2 Hz, IH), 5.31 (AB-q, J = 10.9 Hz, A= 29.0 Hz, 2H), 3.63 (app t, J = 3.5 Hz, IH), 3.03 (dd, J = 9.4, 5.0, IH), 2.85 (dd, J = 5.2, 2.7, IH), 2.14 (s, 3H); LC/MS C-18 column, t = 2.26 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 484 (M+H) and 502 (M+H 3 0). ES-HRMS m/z 502.0273 (M+H 3 0 calcd for C 21 HIvBrF 4 NO 4 requires 502.0272). Example 569 methylpyridin-2(iH)-one Step I: A slurry of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l- (2,6-difluorophenyl)-5-iodo-6-methylpyridin-2(iH)-one (80.0 mg, 0.141 mmol) and benzyl amine (300 mg, 2.80 mmol) was heated to 63 °C and stirred for 1.0 hours until complete disappearance of starting material by LCMS analysis. The reaction mixture was then diluted with ethyl acetate (300 mL) and brine washed (3 X 200 mL). The resulting organic extracts were Na S0 4 dried, filtered, and concentrated in vacuo to a residue that was then subjected to Si0 2 chromatography with ethyl acetate/hexanes (3:7) to furnish a brown solid (60.0 mg, 81%). IH NMR (400 MHz, CDCI 3 ) 6 7.43-7.22 (m, 6H), 7.04 (app t, J = 8.4 Hz, 2H), 5.02 (br t, J = 1.6 Hz, iH), 4.86 (d, J = 5.5 Hz, 2H), 2.37 (s, 3H); LC/MS C-18 column, tr = 3.02 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 531 (M+H) . ES-HRMS m/z 530.9344 (M+H calcd for C 19 HIsBrF 2 IN 2 0 requires 530.9375). Example 570 methyl-5- [(E)-2-phenylethenyl]pyridin-2(IH)-one Step I: To an anhydrous -78 °C solution of -bromostyrene (1.80 g, I0.0 mmol) in ether (18 mL) was added sequentially a solution of zinc chloride (i0.0 mL, 1.0 M ether, i0.0 mmol) over 1.0 minute and a solution of tert-butyl lithium (15.0 mL, 1.6 M pentanes, 24.0 mmol) over 8.0 minutes. The resulting solution became cloudy and the reaction mixture was allowed to warm to room temperature on its own accord (over 30 minutes). After an additional 1.0 hour, the suspension was transferred by syringe directly to a separate vessel containing a solution of 3-bromo-4- [(2,4-difluorobenzyl)oxy]-l-(2,6-difluorophenyl)- 5-iodo-6-methylpyridin-2(IH)-one (1.50 g, 2.64 mmol) and tetrakis(tripheylphosphine)palladium (294 mg, 0.254 mmol) in anhydrous THF (4 niL). This resulting suspension was heated to °C for 40 minutes and cooled to room temperature, whereby it was stirred under a positive pressure of argon for an additional 4.0 hours until complete disappearance of starting material by LCMS analysis. The reaction suspension was subsequently treated with NaHCO] and brine (i00 and 200 mL, respectively). The resulting emulsion was extracted with ethyl acetate (3 X 300 mL) and the organic extracts were Na 2 S0 4 dried, filtered, and concentrated in vacuo to a residue that was then subjected to Si0 2 chromatography with ethyl aceta e/hexanes (3:7) to furnish a reddish solid (1.25 g, 86 %). iH NMR (400 MHz, CDCI ) 8 7.51-7.39 (m, 2H), 7.38-7.24 (m, 5H), 7.10 (app t, J = 8.5 Hz, 2H), 6.84 (d, J = 17.2 Hz, IH), 6.82-6.75 (m, IH) , 6.74-6.68 (m, !H) , 6.69 (d, J = 17.2, IH), 5.11 (br s, 2H) , 2.15 (s, 3H) ; LC/MS C-18 column, tr = 3.74 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 544 (M+H) . ES-HRMS m/z 544. 0565 (M+H calcd for C 27 HI BrF 4 NO 2 requires 544.0530). Example 574 I H O F 4-(allylamino)-3-bromo-l-(2,6-difluorophenyl)-5-iodo-6methylpyridin-2(iH)-one Step i: A slurry of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l- (2,6-difluorophenyl)-5-iodo-6-methylpyridin-2(iH)-one (1.40 g, 2.46 mmol) and allyl amine (1.98 mg, 34.6 mmol) was heated to 50 °C and stirred for 1.0 hours until complete disappearance of starting material by LCMS analysis. The reaction mixture was then concentrated in vacuo (I.0 mm Hg) for 2 days at 50 °C to furnish a brown solid (1.18 g, 99 %). IH NMR (300 MHz, 2.71 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 481 (M+H) ° ES-HRMS m/z 480. 9261 (M+H calcd for C sHI 3 BrF IN 0 O requires 480.9219). Example 575 4-(allylamino)-l-(2,6-difluorophenyi)-5-iodo-6-methylpyridin2(IH)-one Step I: A solution of 4-(allylamino)-3-bromo-l-(2,6difluorophenyl)-5-iodo-6-methylpyridin-2(IH)-one (I.00 g, 2.07 mmol) and tetrakis(tripheylphosphine)palladium (420 mg, 0.363 mmol) in anhydrous THF (i0 mL) under an argon stream was heated to 64 °C and stirred for 12 hours until complete disappearance of starting material by LCMS analysis. The reaction suspension was subsequently treated with brine (600 mL) . The resulting emulsion was extracted with ethyl acetate (3 X 400 mL) and the organic extracts were anhy. Na 2 SO 4 dried, filtered, and concentrated in vacuo to a residue that was then subjected to Si0 2 chromatography with ethyl acetate/hexanes (gradient 3:7) to furnish a solid (376 mg, 45 %). IH NMR (400 MHz, d 4 -MeOH) 6 7.55 (app tt, J = 8.7, 6.3, IH), 7.18 (app t, J = 7.6 Hz, 2H), 5.89 (app ddd, J = 15.4, 10.3, 5.1 Hz, IH), 5.01 (app d, J = 17.0, Hz, IH), 5.50 (s, IH), 5.22 (app d, J = ii.0 Hz, IH), 4.35 (app d, J = 5.0 Hz , 2H), 2.36 (s, 3H) ; LC/MS C-18 column, t= = 2.33 minutes (5 to 95% acetonitrile/water over 5 minutes at I ml/min with detection 254 nm, at 50°C) . ES-MS m/z 403 (M+H). ES-HRMS m/z 403.0133 (M+H calcd for CIsHI 4 F 2 IN 2 0 requires 403.0113). Example 576 4-(allylamino)-l-(2,6-dif!uorophenyl)-5-iodo-6-methylpyridin2(iH)-one Step i: A solution of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l- (2,6-difluorophenyl)-6-methylpyridin-2(IH)- one (197 mg, 0.445 mmol) and allyl amine (1.32 mg, 23.1 mmol) in THF (6.0 mL) was heated to 68 °C and stirred for 74.0 hours. The reaction mixture was then concentrated in vacuo (30 mm Hg) to furnish a residue that was subjected to SiO 2 chromatography with ethyl acetate/hexanes (3:7) to furnish a solid (36.0 mg, 23 %). IH NMR (400 MHz, d 4 -MeOH) 6 7.55 (app tt, J = 8.5, 6.5, IH), 7.18 (app t, J = 8.5 Hz, 2H), 6.14 (s, IH), 5.91 (app dq, J = 11.5, 6.4 Hz, IH), 5.23 (dd, J = 17.0, 1.5 Hz, IH) , 5.19 (dd, J = ii.0, 1.6 Hz, IH), 4.00 (app d, J = 4.7 Hz , 2H), 1.98 (s, 3H); LC/MS C-18 column, tr = 2.24 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 355 (M+H) . ES-HRMS m/z 355.0257 (M+H calcd for CIsHI 4 F 2 BrF 2 N 2 0 requires 355.0252). Example 577 ethyl 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxo-2H1,2'-bipyridine-5'-carboxylate Step I: To a room temperature suspension of 3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one (500.0 mg, 1.51 mmol) and Cs 2 CO 3 (1.50 g, 4.60mmol) in l-methyl-2-pyrrolidinone (3.0 mL) was added ethyl 6-chloronicotinate (900 mg, 4.85 mmol). The resulting suspension was stirred and heated to 106 °C for 36 hours until complete consumption of starting material by LCMS analysis. The reaction mixture was then diluted with ethyl acetate (400 mL), water washed (3 X 200 mL) . The resulting organic extract was separated, Na 2 S0 4 dried, and concentrated. The resulting dark residue was subjected to SiO 2 chromatography with ethyl acetate/hexanes (3:7) to furnish a solid. IH NMR (400 MHz, d 4 -MeOH) 6 8.68 (app d, J = 2.5 Hz, IH), 8.39 (dd, J = 8.7, 2.3 Hz, IH), 7.62 (app q, J = 8.2 Hz, IH), 7.15 (d, O = 8.6 Hz, IH), 7.08 (s, IH), 7.08-6.99 (m, 2H), 5.31 (s, 2H), 4.37 (q, J = 7.1 Hz, 2H), 2.43 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H); LC/MS C-18 column, tr = 3.44 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 479 (M+H). ES-HRMS m/z 479.0401 (M+H calcd for C IHIsBrF 2 N 2 0 4 requires 479.0431). Example 578 methyl ethyl) -6-methyl-2H-l, 2 ' -bipyridin-2-one Step I: To a 0 °C solution of methyl magnesium bromide (3.0 M, 3.5 mL, 10.5 mmol) was added dropwise over 15 minutes a solution of ethyl 3-bromo-4- [ (2,4-difluorobenzyl)oxy]-6methyl-2-oxo-2H-l, 2 ' -bipyridine5 ' -carboxylate (500.0 mg, 1.05 mmol) in THF (4.0 mL). The internal temperature of the reaction was never allowed to exceed 0 °C. The resulting solution was maintained for 30 minutes until complete consumption of starting material by LCMS analysis. Next, a solution of ammonium chloride (saturated aqueous, 160 mL) was added. The reaction mixture was extracted with ethyl acetate (3 X i00 mL) and the resulting organic extracts were separated, Na 2 SO 4 dried, and concentrated in vacuo to a residue that was subjected to SiO 2 chromatography with ethyl acetate/hexanes (gradient 3:7 to 6:4) to furnish a solid (386 rag, 79 %). IH NMR (400 MHz, d 4 -MeOH) 6 8.23 (app d, J = 2.8 Hz, IH), 7.97 (dd, J = 8.6, 2.3 Hz, IH), 7.61 (app q, J = 8.2 Hz, IH), 7.06-7.00 (m, 3H), 7.00 (s, IH), 5.30 (s, 2H), 2.38 (s, 3H), 1.54 (s, 6H); LC/MS C-18 column, tr = 2.75 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 465 (M+H). ES-HRMS m/z 465.0615 (M+H calcd for C 21 H 20 BrF 2 N 2 0 requires 465.0620). IR(neat) 3366, 3030, 2974, 1600, 1507, 1362, 1232 cm -i 13C NMR (400 MHz, d 4 -MeOH, visible peaks with carbon fluorine coupling present) 6 164.4, 160.7, 158.9, 157.6, 143.6, 141.6, 137.5, Example 579 O 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-(2-furylmethyl)-6methylpyridin-2(IH)-one Step I: Preparation of the title compound To a room temperature suspension of 3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methylpyridin-2(iH)-one (330.0 mg, 1.00 mmol)) and NaH (48.0 mg, 2.0 mmol) in THF (3.0 mL) was added 2- (chloromethyl)furan (461 mg, 3.97 mmol). The resulting suspension was stirred and heated to 68 °C for 9 hours until complete consumption of starting material by LCMS analysis. The reaction mixture was then diluted with ethyl acetate (400 mL), water washed (3 X 200 mL). The resulting organic extract was separated, Na 2 S0 4 dried, and concentrated. The resulting dark residue was subjected to SiO 2 chromatography with ethyl acetate/hexanes (4:6) to furnish a solid. IH N-MR (300 MHz, d 4 - MeOH) 6 7.62 (app q, J = 8.4 Hz, IH), 7.46 (s, IH), 7.06 (app t, J = 8.7 Hz, 2H) , 6.51 (s, IH) , 6.41-6.37 (m, 2H) , 5.37 (s, 2H) , 5.32 (s, 2H) , 2.61 (s, 3H) ; LC/MS C-18 column, tr = 2.63 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 410 (M+H) . ES-HRMS m/z 410. 0177(M+H calcd for C 18 HIsBrF 2 NO] requires 410.0198) . Example 580 ob 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyli- (thien-2ylmethyl) pyridin-2 (IH) -one Step I: To a room temperature suspension of 3-bromo-4-[(2,4- difluorobenzyl)oxy]-6-methylpyridin~2(iH)-one (330.0 mg, 1.00 mmol)) and NaH (48.0 mg, 2.0 mmol) in THF (3.0 mL) was added 2-(chloromethyl)thiophene (461 mg, 3.97 mmol). The resulting suspension was stirred and heated to 68 °C for 12 hours until complete consumption of starting material by LCMS analysis. The reaction mixture was then diluted with ethyl acetate (400 mL), water washed (3 X 200 mL). The resulting organic extract was separated, Na 2 SO 4 dried, and concentrated. The resulting dark residue was subjected to Si0 2 chromatography with ethyl acetate/hexanes (4:6) to furnish a solid. IH NMR (400 MHz, d 4 - MeOH) 6 7.58 (app q, J = 8.2 Hz, IH), 7.30 (app dd, J = 5.1, 1.2 Hz, IH), 7.05 (d, J = 2.6 Hz, IH], 7.01 (app t, J = 8.1 Hz, 2H), 6.93 (dd, J = 5.1, 3.4 Hz, IH), 6.43 (s, IH), 5.49 (s, 2H) , 5.25 (s, 2H) , 2.51 (s, 3H) ; LC/MS C-18 column, tr = 2.74 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 426 (M+H) . ES-HRMS m/z 425.9936 (M+H calcd for C 18 HIsBrF 2 N0 2 S requires 425.9969). Example 581 3-bromo-l- (2,6-dif!uorophenyl) -4- (2-furylmethoxy) -6methylpyridin-2 (IH)-one Step i: To a suspension of 3-bromo-4- [(2,4difluorobenzyl)oxy]-l-(2,6-difluorophenyl)-6-methylpyridin2(IH)- one (250 mg, 0.445 mmol) and furfuryl alcohol (198 mg, 2.0 mmol) in THF (2.5 mL) was added solid NaH (46.0 mg, 1.92 mmol). Following the evolution of gas, the resulting suspension laws heated to 60 °C and stirred for 3.5 hours until complete consumption of starting material by LCMS analysis. The reaction mixture was then diluted with ammonium chloride (saturated aqueous, I00 mL) and extracted with ethyl acetate (3 X i00 mL). The resulting organic extracts were separated, Na 2 SO 4 dried, and concentrated to provide a residue that was subjected to SiO 2 chromatography with ethyl acetate/hexanes (3:7) to furnish a solid (Ii0.0 rag, 49 %). IH NMR (400 MHz, d 4 -MeOH) 6 7.63 (app tt, J = 8.5, 6.2, IH), 7.62-7.61 (m, IH), 7.28 (app t, J = 8.5 Hz, 2H), 6.77 (s, IH), 6.68 (d, J = 4.1 Hz, IH), 6.51(dd, J = 4.2, 3.9 Hz, IH), 5.34 (s, 2H), 2.15 (s, 3H); LC/MS C-18 column, tr = 2.43 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 396 (M+H) . ES-HRMS m/z 396.0044 (M+H calcd for CIvHI 3 BrF 2 NO 3 requires 396.0041). Example 582 3-bromo-l- [2fluoro6- (3furylmethoxy) phenyl ] - 4- (3furylmethoxy)-6-methylpyridin-2(iH)-one By following the method of preparation of 3-bromo-l-(2,6difluorophenyl)-4-(2-furylmethoxy)-6-methylpyridin-2(iH)-one (Example 581) and substituting 3-furylmethanol for furfuryl alcohol, the title compound was prepared in 55 % chemical yield. IH N-MR (400 MHz, d 4 -MeOH) 6 7.64 (s, IH), 7.55-7.42 (m, 3H), 7.40 (app t, J = 1.4 Hz, IH), 7.12 (d, J = 9.0 Hz, IH) , 6.92 (app t, J = 8.4 Hz, IH), 6.58 (s, 2H), 6.34 (br s, IH), 5.21 (s, 2H), 5.03 (AB-q, J = 14.0 Hz, A= 58.0 Hz, 2H), 1.99 (s, 3H); LC/MS C-18 column, tr = 2.67 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 474 (M+H). ES~HRMS m/z 474.0346 (M+H calcd for C 22 HIsBrFNOs requires 474.0347). Example 583 3~bromo-l-[2-fluoro-6-(thien-3-ylmethoxy) phenyl]-6-methyI-4- (thien-3-ylmethoxy)pyridin-2(iH)-one By following the method of preparation of 3-bromo-l-(2,6dif!uorophenyl) -4- (2furylmethoxy) -6-methylpyridin-2 (IH) -one Example 581 and substituting thien-3-ylmethanol for furfuryl alcohol, the title compound was prepared in 38 % chemical yield. IH NMR (400 MHz, d 4 -MeOH) 6 7.50-7.42 (m, 3H), 7.33 (dd J = 5.0, 3.0 Hz, IH), 7.26 (br d, J = 2.0 Hz, IH), 7.19 (dd, J = 5.0, 1.2 Hz, IH) , 7.09 (d, J = 8.6 Hz, IH) , 6.98 (dd, J = 14.9, 1.3 Hz, IH) , 6.93 (dt, J = 8.7, !.0 Hz, IH), 6.53 (br s, IH), 5.33 (s, 2H), 5.14 (AB-q, J = 12.1 Hz, A= 50.0 Hz, 2H) 1.97 {s, 3H) ; LC/MS C-18 column, tr = 2.93 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 506 (M+H) . ES-HRMS m/z 505.9881 (M+H calcd for CnHIsBrFNO 3 S 2 requires 505.9890). Example 584 methyl 2-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-4-[(methylamino)carbonyl]benzoate Step i: Preparation of 3-(4-hydroxy-6-methyl-2-oxopyridinl(2H)-yl)-4-(methoxycarbonyl)benzoic acid 4-Hydroxy-6-methyl-2-pyrone (75.0 g, 595 mmol) and 3amino-4-(methoxycarbonyl)benzoic acid (40.0 g, 0.205 mmol) were suspended in 56 ml of 1,2-dichlorobenzene in a 500 ml, 3necked, round bottom flask equipped with a J-Kem temperature controller probe, a Dean-Stark trap, and a heating mantle. The reaction was heated to 180 °C over a period of 26 minutes during which time all solids dissolved. Upon reaching an internal temperature of 180 °C, the reaction was allowed to maintain this temperature for an additional 25.0 minutes during which time the evolution of water from the reaction mixture was evident. Next, the heating apparatus was removed and the reaction was allowed to cool on its own accord to about i00 °C. The reaction was then diluted with 160 ml of toluene and stirred. After about i0 minutes, the reaction reached room temperature and a gummy solid had formed. The precipitate was filtered, washed with EtOAc (400 mL) and water (200 mL, 55 °C), and dried in vacuo to give a tan solid (30.5 g, 49%). IH NMR (400 MHz, d -MeOH) 5 8.20-8.09 (m, 2H), 7.84 (s, IH), 6.08 (app d, J = 1.0 Hz, IH), 5.76 (app d, J = 2.3 Hz, IH), 3.76 (s, 3H), 1.91 (s, 3H) . LC/MS, C-18 column, tr = 1.96 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50 °C). ES-MS m/z 304 (M+H) . ES-HRMS m/z 304.0803 (M+H calcd for C 15 HI 4 NO requires Step 2: Preparation of methyl 2-(4-hydroxy-6-methyl-2oxopyridin-l(2H)-yl)-4-[(methylamino)carbonyl]benzoate OH H O To a solution of 3-(4-hydroxy-6-methy!-2-oxopyridin- l(2H)-yl)-4-(methoxycarbony!)benzoic acid ( from Step i) (I.00 g, 3.30 mmol) in dimethylformamide (i0 mL) and THF (I0 mL) was added cyclohexylcarbodiimide-derivatized silica gel (a product of Silicycle chemical division Quebec, Canada) with a loading of 0.60 mmol/g (15.2 g, 9.73 mmol). After stirring for minutes, a solution of methylamine (2.0 M, THF, 2.9 mL, 5.8 mmol) was added followed by the addition of l-hydroxybenzotriazole (20.0 mg, 0.15 mmol) . The reaction suspension was allowed to stir for 24 hours until the complete disappearance of starting material by LCMS analysis. The silica suspension was filtered and washed with 300 mL ethyl acetate/methanol (9:1) and 300 niL ethyl acetate/methanol (i:i) . The resulting mother liquor was concentrated to furnish a brown semi-solid (898 mg, 86 %). IH NMR (300 MHz, d 4 -MeOH) 6 8.22 (d, J = 8.0 Hz, IH), 8.04 (dd, J = 8.3, 1.9 Hz, IH), 7.73 (d, J = 1.6 Hz, IH), 6.13 (d, J = 1.5, Hz, IH), 5.80 (d, J = 2.2 Hz, IH), 3.80 (s, 3H), 3.03 (s, 3H), 1.97 (s, 3H) . LC/MS, C-18 column, tr = 1.31 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 317 (M+H). ES-HRMS m/z 317.1142 (M+H calcd for CIGHI N 2 Os requires 317.1132). Step 3: Preparation of 2-oxopyridin-l(2H)-yl)-4- methyl 2-(3-bromo-4-hydroxy-6-methyl- [(methylamino)carbonyl]benzoate To a room temperature suspension of methyl 2-(4-hydroxy6-methyl-2-oxopyridin1 (2H) -yl) -4- [(methylamino)carbonyl]benzoate ( from Step 2) (406.0 rag, 1.28 mmol) in CH 2 C1 2 (8 mL) was added solid N-bromosuccinimide (251 mg, 1.41 mmol) and stirred for i0 minutes until complete consumption of starting material by LCMS analysis. The reaction was next diluted with CH 2 C1 2 (5 mL), ethyl acetate (5 mL) , and hexanes (I mL) . After approximately 30 minutes the resulting white precipitate was filtered and washed with ethyl acetate (5 mL) to furnish a solid (298 mg, 62%). IH NMR (400 MHz, d 4 -MeOH) 6 8.20 (d, J = 8.2 Hz, IH), 8.01 (d, J = 8.1 Hz, IH), 7.69 (s, IH), 6.18 (s IH), 3.75 (s, 3H), 2.91 (s, 3H), 1.91 (s, 3H) ; LC/MS, tr = 1.27 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 395 (M+H). ES-HRMS m/z 395.0237 (M+H calcd for C 16 HI BrN 2 0 5 requires 395.0237). Step 4 : Preparation of the title compound . To a solution of methyl 2-(3-bromo-4-hydroxy-6-methyl-2oxopyridin-! (2H) -yl) -4- [ (methylamino)carbonyl] benzoate ( from Step 3) (241 mg, 0.610 mmo!) in dimethylformamide (0.5 mL) was added sequentially K 2 C0 3 (240 mg, 1.73 mmo!) and 2,4 dif!uoroben--yl bromide (0 . 085 mL, 0.66 mmol) . The resulting suspension was stirred for 6.5 hours until complete consumption of starting material by LCMS analysis. The reaction was then diluted with ethyl acetate (200 mL) and brine washed (3 X 200 mL) . The resulting organic extract was Na 2 S0 4 dried, filtered, and concentrated in vacuo to approximately 5 mL volume. The resulting mother liquor rapidly precipitated and furnished an amorphous solid that was collected. IH NMR (400 MHz, d 4 -MeOH) 6 8.22 (d, J = 8.2 Hz, IH) , 8.03 (dd, J = 8.2, 1.7 Hz, IH) , 7.71 (d, J = 1.8 Hz, IH) , 7.67 (app q, J = 8.3 Hz, IH), 7.05 (app t, J = 8.6 Hz, 2H), 6.64 (s, IH) , 5.37 (s, 2H) , 3.74 (s, 3H) , 2.90 (s, 3H) , 2.01 (s, 3H) . LC/MS C-18 column, tr = 2.87 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 521 (M+H) . ES-HRMS m/z 521.0491 (M+H calcd for C 23 H 20 BrF 2 N 2 Os requires 521.0518). Example 585 3 - [3 -bromo4 - [ (2,4 -di f luorobenzyl ) oxy] -6-methyl -2 - oxopyridin1 (2H) -yl] -4- (l-hydroxy-l-methylethyl) -N-methylbenzamide Step I: To a -i0 °C solution of methyl magnesium bromide (3.0 M, 0.60 mL, 1.8 mmol) was added dropwise over i0 minutes a solution of methyl 2- [3-bromo-4- [ (2,4-difluorobenzyl)oxy]-6methyl -2-oxopyridin1 (2H) -yl ] -4- [(methylamino) carbonyl]benzoate (85.0 mg, 0.163 mmol) in THF (I.0 mL). The internal temperature of the reaction was never al!owed to exceed 0 °C. The resulting solution was maintained for i0 minutes. Next, a solution of ammonium chloride (saturated aqueous, i00 mL) was added. The reaction mixture was removed from the bath and resulting emulsion was extracted with ethyl acetate (3 X I00 mL) and the resulting organic extracts were separated, Na 2 SO 4 dried, and concentrated in vacuo to a residue that was subjected to Si0 2 chromatography with ethyl acetate/hexanes (gradient 3:7 to 6:4) to furnish a solid (16 rag, 19 %). IH NMR (400 MHz, d 4 -MeOH) 6 7.89 (d, J = 8.5 Hz, IH), 7.78 (d, J = 8.4 Hz, IH), 7.61 (app q, J = 8.2 Hz, IH), 7.41 (s, IH), 7.03-6.99 (m, 2H) , 6.57 (s, IH), 5.30 (s, 2H), 2.83 (s, 3H), 2.05 (s, 3H), 1.51 (s, 3}4), 1.39 (s, 3H) ; LC/MS C-18 column, tr = 2.28 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 521 (M+H) . ES-HRMS m/z 521.0860 (M+H calcd for C 24 H 24 BrF 2 N 2 0 4 requires 521.0882). Example 586 3-bromo-l- [2fluoro6- (thien-3-ylmethoxy) phenyl] - 6-methyl-4- (thien-3 -ylmethoxy) pyridin2 (IH) -one By following the method of preparation of 3-bromo-l-(2,6difluorophenyl) -4- (2furylmethoxy) -6-methylpyridin-2 (IH) -one Example 581 and substituting 4- { [3-bromo-4- [ (2,4difluorobenzyl) oxy] - 6-methyl2-oxopyridin1 (2H) - yl]methyl}benzamide for 3-bromo-4-[(2,4~difluorobenzyl)oxy] - I- (2,6-difluorophenyl)-6-methylpyridin-2 (IH) - one , the title compound was prepared in 76 % chemical yield. IH NMR (400 MHz, d 4 -MeOH) 6 7.83 (d, J = 8.1 Hz, 2H), 7.54 (app d, J = I.i Hz, IH), 7.19 (d, J = 8.1 Hz, 2H), 6.57 (d, J = 3.2 Hz, IH) , 6.53 (s, IH), 6,43 (dd, J = 3.1, 1.8 Hz, IH), 5.45 (br s, 2H) , 5.22 (S, 2H) , 2 34 (s, 3H) ; LC/MS C-18 column, tr = 1.98 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 417 (M+H) . ES-HRMS m/z 417. 0469 (M+H calcd for C 19 HIsBrN 2 0 4 requires 417.0444 Example 587 (-)-3- [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin1 (2H) -yl] -N, 4-dimethylbenzamide Example 489 (1.78 g, 4.36 retool) were separated using a Chiral Technologies Chiralpak AD column (21 mm x 250 mm, 20 m) eluting with 100% ethanol (isocratic 0 20 ml/min), loading I0 mg per injection. Fractions of the early-eluting atropisomer were pooled and concentrated in vacuo to the title compound (718 rag, 80%). Analytical chiral LC (Chiralpak AD, 4.6 mm x mm, 10 m particle size, 0.5 ml/min ethanol) Retention time: 1.70 rain, ee 94%. [0 D = -23.8° (5 mg/ml DMSO, 22 °C). IH NMR (400 MHz, DMSO-d 6 ) 6 8.42 (br qr, J = 4.51 Hz, IH) , 7.82 (dd, J = 7.92, 1.70 Hz, IH) , 7.68 (dt, J = 8.24, 6.58 Hz, IH) , 7.58 (d, J = 1.59 Hz, IH), 7.48 (d, J = 7.98 Hz, IH), 7.34 (dt, J = 9.90, 2.50 Hz, IH), 7.18 (dt, J = 8.53, 2.57 Hz, IH), 6.71 (s, IH) , 5.33 (s, 2H), 2.74 (s, 3H) , 1.98 (s, 3H), 1.88 (s, 3H) . 19F-NMR (400 MHz, DMSO-d ) 6-109.58 (quintet, J = 7.49 Hz, IF), -113.65 (quartet, J = 9.11 Hz, IF). ES-HRMS m/z 477.0612 (M+H calcd for C 22 H 20 BrF 2 N 2 0 3 requires 477.0620). Example 588 oxopyridin1 (2H) -yl ] -N, 4-dimethylbenzamide The title compound was prepared as in Example 587 , pooling the late-eluting atropisomer (722 mg, 81%). Analytical chiral LC (Chiralpak AD, 4.6 mm x 50 mm, 10#m particle size, 0.5 ml/min ethanol) Retention time: 2.00 min, ee 98%. [( D = +28.2° (5 mg/ml DMSO, 22 °C) . IH NMR (400 MHz, DMSO-d ) 6 8.42 (br qr, J = 4.51 Hz, IH), 7.82 (dd, J = 7.92, 1.70 Hz, IH), 7.68 (dr, J = 8.24, 6.58 Hz, IH) , 7.58 (d, J = 1.59 Hz, IH), 7.48 (d, O = 7.98 Hz, IH), 7.34 (dt, J = 9.90, 2.50 Hz, IH) , 7.18 (dt, J = 8.53, 2.57 Hz, IH) , 6.71 (s, IH) , 5.33 (s, 2H), 2.74 (s, 3H), 1.98 (s, 3H), 1.88 (s, 3H) . 19F-NMR (400 MHz, DMSO-d ) 6 -109.58 (quintet, J = 7.49 Hz, IF), 113.65 (quartet, J = 9.11 Hz, IF). ES-HRMS m/z 477.0614 (M+H calcd for C 22 H 20 BrF 2 N 2 0 requires 477.0620). Example 589 F Cl NH 2 4- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2 ~oxopyridin1 (2H) -yl] -3-chlorobenzamide Step i: Preparation of methyl 3-chloro-4-(4-hydroxy-6-methyl2 -oxopyridin1 (2H) -yl) benzoate CI O OCH 3 4-Hydroxy-6-methyl-2-pyrone(24.5 g, 193.9 mmol) and methyl-3-amino-2-chlorobenzoate(30 g, 161.6 mmol) were suspended in 75 ml of 1,2-dichlorobenzene in a 250 ml, 3necked round bottom flask equipped with a J-Kem temperature controller probe, a Dean-Stark trap, and a heating mantle. The reaction was heated to 175°C for 20 minutes, during which, water and some 1,2-dichlorobenzene was collected in the DeanStark trap. The reaction was allowed to cool to about II0°C. At this point, 200 ml of toluene was added. The toluene mixture was allowed to stir for 72 hours at room temperature. A precipitate was collected on a filter pad. The precipitate was filtered and washed 3 times with toluene, 3 times with 50°C. water to remove excess pyrone, and dried in vacuo to give a tan solid (13.0 g, 27% yield). IH NMR (300 MHz, CD 3 OD) 6 8.26 (d, J = 1.81 Hz, IH), 8.14 (dd, J = 8.26, 1.81 Hz, IH), 7.54 (d, J = 8.26, Hz, IH), 6.14(dd, J = 2.42, 1.0 Hz, IH), 5.83 (d, J = 2.42 IH), 4.00 (s, 3H), 1.96 (s, 3H) ; LC/MS, tr = 1.81 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 294 (M+H) . Step 2: Preparation of methyl 3-chloro-4- [4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]benzoate Methyl 3-chloro-4-(4-hydroxy-6-methyl-2-oxopyridin-l(2H)- yl)benzoate ( from Step i) (2.4g, 8.17 mmol) was taken up in DMF (I0 ml) . 2,4-difluorobenzylbromide (1.05 ml, 8.17 mmol) and K=C0 3 (1.13 g, 8.17 mmol) were added. The reaction stirred for 6 hours at room temperature. At this time, the reaction was poured into water (200 ml) and extracted with ethyl acetate. The ethyl acetate layer was dried over Na 2 SO 4 , filtered, and the solvent removed in vacuo to give amber oil (2.62 g, 77% crude yield). LC/MS, tr = 2.79 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 294 (M+H) . Step 3; Preparation of methyl 4-[3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-3chlorobenzoate c OCH 3 Methyl 3-chloro-4-[4-[(2,4-difluorobenzyl)oxy]-6-methyl2-oxopyridin-l(2H)-yl]benzoate ( from step 2) (2.60g, 6.21 mmol) was taken up in CH 2 C1 2 (20 ml). N-bromosuccinimide (l.llg, 6.21 mmol) was added and the mixture stirred at room temperature for 4 hours. The CH 2 C1 2 is removed in vacuo and the residue is taken up in CH 3 CN. The resulting precipitate is collected on a filter pad and washed with CH 3 CN to yield a white solid (0.75 g, 24%). IH NMR (300 MHz, CDCI 3 ) 5 8.22 (d, J = 1.88 Hz, IH), 8.06 (dd, J = 8.19, 1.75 Hz, IH), 7.59 (app q, J = 8.46 Hz, IH), 7.33 (d, J = 8.19, IH), 6.96 (dt, J = 8.06, 1.21 Hz, IH), 6.89 - 6.84 (m, IH), 6.13 (s, IH), 5.26 (s, 2H) , 3.95 (s, 3H) , 1.95 (s, 3H) ; ES-MS m/z 478 (M+H) . ESHRMS m/z 497. 9892 (M+H calcd for C 22 HI 6 BrCIF 2 NO 4 requires 497.9914). Step 4: Preparation of 4- [3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-3chlorobenzoic acid . O OH Methyl-4-[3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-3-chlorobenzoate (2.30g, 4.61 mmol) was taken up in THF (20 ml) and H 2 0 (4 ml). 2.5 N NAOH (9.2 ml) was added to the vessel and the reaction stirred overnight to completion. Concentrated HCI was added dropwise until reaction was made acidic (pH = I). H 2 0 (i00 ml) and THF (i00 ml) were added to the mixture. The contents were poured into a separatory funnel and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over Na 2 S0 4 , the solvent removed in vacuo, and the residue was taken up in a 50% mixture of ethyl acetate/hexane. The precipitate was collected on a filter pad to yield a white powder (l.5g, 67%). 1.96 (s, 3H) ; ES-MS m/z 483 (M+H) . calcd for C 20 HI 4 BrClF 2 NO 4 requires ES-HRMS m/z 483.9749 (M+H 483.9757). Step 5: 4- [3-Bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-3-chlorobenzoic acid (0.5 g, 1.03 retool) was taken up in THF (i0 ml) . 2-Chloro-4,6-dimethoxy-l,3,5- triazine (0.22 g, 1.24 retool) and N-methyl morpholine (0.34 ml, 3.09 mmol) were added. The mixture stirred at room temperature for 1 hour. At this time, NH 4 0H (2.5 ml) was added and the reaction stirred at room temperature for one more hour. To the reaction mixture was added more THF (50 ml) and water (200 ml). The mixture was extracted with ethyl acetate. The ethyl acetate extraction was washed with saturated brine solution. The brine layer was extracted with ethy! acetate. The organic layers were combined, dried over Na 2 S0 4 , filtered and the solvent was removed in vacuo. The residue was taken up in ethyl acetate and the resulting precipitate was collected on a filter pad to yield a white powder (0.38 g, 76%) IH NMR (300 MHz, CODED) 6 8.18 (d, J = 1.81 Hz, IH), 8.02 (dd, J = 8.26, 2.01 Hz, IH), 7.69 (app q, J = 8.26 Hz, IH), 7.55 (d, J = 8.06 Hz, 1 H) 7.12 - 7.06 (m, 2H), 6.71 (s, IH), 5.40 (s, 2H), 2.07 (s, 3H). ES-MS m/z 482 (M+H). ES-HRMS m/z 482.9919 (M+H calcd for C 20 HIsBrCIF 2 N 0 3 requires 482.9917). Example 590 O NH 2 3- [3chloro-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl2-oxopyridin1 (H) -yl] -4-methylbenzamide Stepl: Preparation of 3-[3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4methylbenzoic acid O 3-[4-[(2,4-Difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-4-methylbenzoic acid ( from above) (7.5g,19.4 mmol) and NCS (2.6 g, 19.4 mmol) were taken up in 65°C dichloroethane (i00 ml). A catalytic amount of dichloroacetic acid (2 drops) was added. After two hours the solvent was removed in vacuo and the residue was taken up in diethyl ether. The precipitate was collected on a filter pad and then taken up in 50% ethyl acetate/hexanes to remove residual succinimide. The precipitate was collected on a filter pad and then dried in vacuo to produce a white powder (4.2 g, 52%). IH NMR (300 MHz, (S, 3H) , 2.04 (s, 3H) ; ES-MS m/z 420 (M+H) . ES-HRMS m/z 420.0786 (M+H calcd for C IHITCIF 2 NO 4 requires 420.0809). Step 2: 3-[3-chloro-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2- oxopyridin-l(2H)-yl]-4-me hylbenzoic acid ( 1.5g, 3.57 mmol) was taken up in THF (30 ml). 2-Chloro-4,6-dimethoxy-l,3,5triazine (0.75 g, 4.28 mmol) and N-methyl morpholine (1.18 ml, 10.72 mmol) were added. The mixture stirred at room temperature for 1 hour. At this time, NH 4 0H (7.5 ml) was added and the reaction stirred at room temperature for one more hour. To the reaction mixture was added more THF (!00 ml) and water (150 ml). The mixture was extracted with ethyl acetate. The ethyl acetate extraction was washed with saturated brine solution. The brine layer was extracted with ethyl acetate. The organic layers were combined, dried over Na 2 S0 4 , filtered and the solvent was removed in vacuo. The residue was taken up in ethyl acetate and the resulting precipitate was collected on a filter pad to yield a white powder (1.32 g, 88%) H NMR (300 MHz, CD 3 OD) 6 7.96 (dd, J = 7.85, 1.81 Hz, IH), 7.71 (d, J = 1.81 Hz, IH), 7.67 (app q, J = 8.06 Hz, IH}, 7.56 (d, J = 8.06 Hz, IH) , 7.12 - 7.06 (m, 2H) , 6.74 (s, IH) , 5.40 (s, 2H) , 2.13 (s, 3H) 2.05 (s, 3H) . ES-MS m/z 419 (M+H) . ES-HRMS m/z 419.0979 (M+H calcd for C 21 HIsCIF 2 N 2 0 3 requires 419.0969). Example 591 3- [3-chloro-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-N,4-dimethylbenzamide The title compound was prepared from 3- [3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4methylbenzoic acid ( from step 1 above) (1.5 g, 3.57 mmol) in dichloromethane (35 ml). To this mixture, 2.0 M methyl amine in THF (3.6 ml, 7.14 mmol) was added, followed, in order, by EDCI (0.67 g, 4.28 mmol), l-hydroxybenzotriazole (0.58 g, 4.28 mmol) and tr: :hylamine (0.99 ml, 7.14 mmol). The reaction was stirred at room temperature overnight. The reaction was quenched with NH 4 CI and extracted 3 times with ethyl acetate. The combined organic layer was then washed with saturated NaHC0 3 (aq.) and extracted 3 times with ethyl acetate. The organic layers were combined and washed with H 2 0 and extracted 3 times with ethyl acetate. The organic layers were combined and dried over Na 2 SO 4 and evaporated. The resulting residue was triturated with diethyl ether/hexane to obtain a solid, which was dried in vacuo to give a white solid (l.5g, 72%). IH NMR (300 MHz, CD 3 OD) 6 7.90 (dd, J = 8.06, 1.81 Hz, IH), 7.67 (app q, J = 6.44 Hz, IH), 7.55 (d, J = 8.06 Hz, IH), 7.13 - 7.06 (m, 2H) , 6.74 (s, IH) , 5.40 (s, 2H) , 2.93 (s, 3H) , 2.13 (s, 3H) , 2.04 (s, 3H) ES-MS m/z 433 (M+H) . ES-HRMS m/z 433.1153 (M+H calcd for C 2 H 20 CIF 2 N 2 0 requires 433.1125). Example 592 H O N- {3- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl] -4fluorobenzyl }propanamide A i0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with I-[5-(aminomethyl)-2fluorophenyl]-3-chloro-4- [(2,4 difluorobenzyl)oxy]-6methylpyridin-2(1H)-one hydrochloride (250 mg, 0.56 mmol), propionyl chloride (49 L, 0.56 mmol), triethylamine (195 L, 1.4 mmol) and tetrahydrofuran (4.0 mL) . After stirring at 25° C for 5 min the reaction was completed by LC-MS. The reaction mixture was poured into a saturated aqueous NH 4 CI solution. The aqueous mixture was extracted with ethyl acetate. The organic phase was dried with Na 2 SO 4 and concentrated in vacuo to obtain (240 rag, 91%) as a yellow solid. IH NMR (400 MHz, (CD 3) 2 SO) 6 8.3 (t, J = 5.8 Hz, IH), 7.6 (q, J = 8.7 and 6.58 Hz, IH) , 7.38 (d, J = 7.78 Hz, IH), 7.3 (dd, J = 2.6 and 7.6 Hz, IH) , 7.22 (d, J = 7.51 Hz, IH), 7.12 (td, J = 2.0 and 6.5 Hz, IH) , 6.65 (s, IH), 5.3 (s, 2H) , 4.23 (d, J = 3.6 Hz, 2H), 2.1 (q, J = 7.7 Hz 2H), 1.98 (s, 3H), 0.98 (t, J = 7.5 Hz, 3H) ppm. ES-HRMS m/z 465.1203 (M+H calcd for C 23 H 21 CIF 3 N 2 0 3 requires Example 593 O N-{3- [3-chloro-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-4-fluorobenzyl} dimethylurea A i0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with l-[5-(aminomethyl)-2fluorophenyl]-3-chloro-4- [(2,4 difluorobenzyl)oxy]-6- methylpyridin-2(iH)-one hydrochloride (250 mg, 0.56 mmol), dimethylcarbamyl chloride (52 L, 0.56 mmol), triethylamine (195 L, 1.4 mmol) and tetrahydrofuran (4.0 mL). After stirring at 25° C for 5 min the reaction was completed by LC-MS. The reaction mixture was poured into a saturated aqueous NH 4 CI solution. The aqueous mixture was extracted with ethyl acetate. The organic phase was dried with Na 2 S0 4 and concentrated in vacuo to obtain the desired product (245 mg, 86%) as a white solid. IH NMR (400 MHz, (CDHOD) 6 7.61 (q, J = 7.9 and 6.7 Hz, IH), 7.4(m, IH), 7.3 (d, J = 9.3 Hz, IH), 7.21 (m, IH), 7.1 (m, 2H), 6.65 (s, IH), 5.35 (s, 2H), 4.38 (s, 2H), 2.9 (s, 6H), 2.1 (s, 3H) ppm. ES-HRMS m/z 480.1269 (M+H calcd for C 23 H 22 CIF 3 N 3 0] requires 480.1296). Example 594 N-{3- [3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-4-fluorobenzyl}-2-hydroxyacetamide A i0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with I- [5-(aminomethyl)-2fluorophenyl]-3-chloro-4- [(2,4 difluorobenzyl)oxy]-6methylpyridin-2(IH)-one hydrochloride (250 mg, 0.56 mmol) , acetoxyacetyl chloride (66 ML, 0.62 mmol), triethylamine (195 ML, 1.4 mmol) and tetrahydrofuran (4.0 mL) . After stirring at 25° C for 5 min the reaction was completed by LC-MS. NaOH (2.5M, 2.24 mmol, 1.0 mL) and MeOH (2.0mL) was added and stirred for I0 min to give the title compound. The reaction mixture was acidified with concentrated HCI and extracted with ethyl. The organic phase was dried with Na 2 SO 4 and concentrated in vacuo to obtain (217 mg, 78%) of the desired product as a yellow solid. IH NMR (400 MHz, (CD 3 OD) 6 7.6 (q, = 7.6 and 6.9 Hz, IH) , 7.44 (m, IH) , 7.34 (m, 2H) , 7.22 (m, 2H), 6.63 (s, IH), 5.35 (s, 2H) , 4.41 (s, 2H), 4.0 (s, 2H) , 2.05 (s, 3H) ppm. ES-HRMS m/z 467.0957 (M+H calcd for C 22 HIgCIF 3 N 2 0 4 requires 467.0980). Example 595 F .CI H O N- {3- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl] -4fluorobenzyl } -2-hydroxy2- methylpropanamide The title compound was prepared essentially as described Example 594, with l-chlorocarbonyl-l-methylethyl acetate substituting acetoxyacetyl chloride IH N-MR (400 MHz, (CDCI 9.9 (q, J = 8.2 and 6.5 Hz, IH), 9.7 (t, J = 2.6 Hz, IH), (t, J = 8.9 Hz, 2H), 9.3 (m, IH), 9.2 (m, IH) , 8.6 (s, IH) (s, 2H), 6.8 (d, J = 15 Hz, IH), 6.63 (d, J = 15 Hz, IH), (d, J = 3.2 Hz, 6H), 3.99 (s, 3H) ppm. ES-HRMS m/z 495.1271 (M+H calcd for C 24 H 23 CIF 3 N 2 0 4 requires 495.1293). Example 596 N I- {3- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6 -methyl -2oxopyridin-l(2H)-yl]-4-fluorobenzyl}glycinamide hydrochloride A 25 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with boc-glycine (105 mg, 0.6 mmol) and 8 mL of DMF. The mixture was cooled to 0° C and isboutylchloroformate (77.5 L, 0.6 mmol) was added and stirred for 20 min. I- [5-(aminomethyl)-2-fluorophenyl]-3-chloro-4- [(2,4 difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one hydrochloride (250 mg, 0.6 mmol) was added and stirred for 3h. After completion of the reaction by LC-MS, concentrated HCI (2 niL) and 2 mL of methanol was added to remove the boc group. The reaction was stirred for 24 h, neutralized with 2M NaOH and extracted with ethyl acetate. The organic phase was dried with Na 2 SO 4 and concentrated in vacuo to obtain (196 mg, 66%) of the desired product as a the HCI salt. IH NMR (400 MHz, (CD 3 OD) 6 7.6 (q, J = 8 and 6.5 Hz, IH), 7.5 (m, IH), 7.3 (m, 2H), 7.0 (m, 2H), 6.63 (s, IH), 5.35 (s, 2H), 4.4 (q, J = and 13.6 Hz, 2H), 3.7 (s, 2H), 2.05 (s, 3H) ppm. ES-HRMS m/z 466.1157 (M+H calcd for C 22 H 20 CIF 3 N 3 0 3 requires 466.1140). Example 597 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl2-oxopyridin1 (2H) -yl] -4fluorobenzamide A 250 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with 3- [3-bromo-4- [ (2,4difluorobenzyl) o×y] -6-methyl-2-oxopyridin1 (2H) -yl] -4fluorobenzoic acid (3.65g, 7.8 mmol), 4-methylmorpholine (2.6 mL, 23.4 mmol), 2-chloro-4,6-dimethoxy-l,3,5-triazine (1.64g, 9.36 mmol) and tetrahydrofuran (40 mL). After stirring the mixture for 30 min at 25° C, NH 4 0H (20.0 mL) was added. The mixture was stirred for 30 min and diluted with water. The product precipitated from solution. The precipitated was filtered and washed with water and diethyl ether to give the title compound (2.37g, 65%) as a white solid. IH NMR (400 MHz, (CD 3) 2 SO) 6 7.9 (d, J = 7.3 Hz, IH), 7.61 (q, J = 8.6 and 6.7 Hz, IH), 7.5 (m, 2H), 7.3 (t, J = 9.6 Hz, IH), 7.15 (t, J = 8.7 Hz, IH), 6.7 (s, IH), 5.36 (s, 2H), 2 (s, 3H) ppm. ES- HRMS m/z 469.0172 (M+H calcd for C 20 HIsBrF 3 N 2 0 3 requires 469.0195). Example 598 F .Br F "0 H I 3- [3-bromo~4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl ] - 4 - f luoro-N-methylbenzamide A solution of 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]-4-fluorobenzoic acid (I g, 2.1 mmol) in N,N-dimethylformamide (20 mL) was cooled to -i0 C. Isobutyl chloroformate (0.27 mL, 2.1 mmol) and N-methyl morpholine (0.23 mL, 2.1 mmol) were added to the reaction vessel. After stirring at -i0 C for 20 minutes, a solution of N-methyl amine (2.1 mL, 4.2 mmol, 2 M in THF) was added and the reaction mixture was warmed to room temperature as it stirred for 18 hours. The reaction mixture was concentrated in vacuo, suspended in water, filtered and washed with water, ethyl acetate and diethyl ether. =H NMR (400 MHz, CODED) 6 8.03 (dddd, J = 3.0, 6.4, 9.2 and 11.6 Hz, IH) , 7.81 (dd, J = 3.0 and (.2 Hz, IH), 7.66 (q, J = 10.4 Hz, IH) , 7.47 (t, J = 12 Hz, IH), 7.06 (t, J = 12 Hz, 2H), 6.67 (s, IH), 5.38 (s, 2H) , 2.91 (s, 3H) , 2.10 (s, 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6 -iii.50 (IF), -115.97 (i F), -120.16 ppm. ES-HRMS m/z 481.0346 (M+H calcd for C 21 HITBrF 3 N 2 0 3 requires 481.0369). Example 599 Br F 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl ] -4 - f luoro-N, N-dimethylbenzamide A solution of 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]-4-fluorobenzoic acid (i g, 2.1 mmol) in N,N-dimethylformamide (20 mL) was cooled to -I0 C. Isobutyl chloroformate (0.27 mL, 2.1 mmol) and N-methyl morpholine (0.23 mL, 2.1 mmol) were added to the reaction vessel. After stirring at -I0 C for 20 minutes, a solution of N-methyl amine (2.1 mL, 4.2 mmol, 2 M in THF) was added and the reaction mixture was warmed to room temperature as it stirred for 18 hours. The reaction mixture was concentrated in vacuo and partitioned between water and ethyl acetate. The organic layer was washed with brine and concentrated in vacuo. The solid was chromatographed on silica (95:5 methylene chloride : isopropyl alcohol) to give the desired product as white powder (0.31 g, 30 %). IH NMR (400 MHz, CD 3 OD) 6 7.64 (m, IH), 7.50 (dd, J = 2.4 and 7.2 Hz, IH), 7.45 (t, J = 9.6 Hz, IH), 7.04 (t, J = 9.2 Hz, 2H), 6.65 (s, IH), 5.36 (s, 2H), !9 3.09 (s, 3H), 3.05 (s, 3H), 2.10 (s, 3H) ppm. F NMR (400 MHz, CD 3 OD) 6-111.51 (IF), -115.88 (I F), -121.90 (IF) ppm. ES-HRMS m/z 495.0508 (M+H calcd for C 22 HIgBrF 3 N 2 0 3 requires 495.0526). Example 600 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -i- {2-fluoro-5- [ (4methylpiperaz in1-yl ) carbonyl ] phenyl } - 6 -methylpyridin2 (1H) - one step i Preparation of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l- {2-fluoro-5- [(4-methylpiperazin-l-yl)carbonyl]phenyl}-6methylpyridin-2(iH)-one To a reaction vessel (borosilicate culture tube) was added 3- [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-4-fluorobenzoic acid (0.300 g, 0.623 mmol) and l-hydroxybenzotriazole (0.042 g, 0.45 mmol) . N,NDimethylformamide (3 mL) was added to the reaction vessel followed by approximately i.I g of the polymer bound carbodiimide resin (1.38 mmol/g) . Additional N,Ndimethylformamide (2 mL) was then added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker at approximately 200 RPM at room temperature for 15 minutes. N-Methyl amine (i mL, 2 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with tetrahydrofuran (20 mL) and treated with approximately 2.0 g of polyamine resin (2.63 mmol/g) and approximately 2.5 g of methylisocyanate functionalized polystyrene (1.5 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature for 3 hours. The reaction vessel was then opened and the solution phase product was separated from the insoluble quenched byproducts by filtration and collection into a vial. After partially evaporation the insoluble byproducts were rinsed with tetrahydrofuran (2 x i0 mL) . The filtrate was evaporated by blowing N 2 over the vial and the resulting solid was triturated with diethyl ether to give an off-white solid. (0.14g, 41%) 115.72 (i F), -121.41 (! F) ppm. ES-HRMS m/z 550.0946 (M+H calcd for C 2 sH 24 CIF 3 N 0 3 requires 550.0948). Example 601-603 .Sr F By following the method of Example 600 and replacing Nmethylamine with the appropriate amine, the compounds of Examples 601-603 are prepared. Compound % M+H ESHRMS No. RI R 2 Yield MF Requires m/z Example 604 C0 2 CH 3 methyl 4- [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-3-fluorobenzoate Step 1 Preparation of 4-amino-3-fluorobenzoic acid NH 2 CO H 3-Fluoro-4-aminobenzoic acid was prepared as described in the literature. (Schmelkes, F.C.; Rubin, M. J. Am. Chem. Soc. 1944, 66, 1631-2.) Step 2 Preparation of methyl 4-amino-3-fluorobenzoate NH 2 CO 2 Me A 250 niL 3-necked round bottomed flask equipped with a nitrogen inlet, stirbar, addition funnel and thermocouple was charged with 4-amino-3-fluorobenzoic acid (11.8 g, 76 mol) and methanol (i00 mL). The system was cooled to 0 C and acetyl choride (7.6 mL, 107 mol) was added dropwise. The system was warmed to room temperature, the addition funnel was replaced with a reflux condensor, and was heated to reflux for 6 h. The reaction mixture was cooled to room temperature, quenched with saturated aqueous NaHCO and extracted with ethyl acetate. The organic extract was washed with bl-ine and concentrated in vacuo to give methyl methyl 4-amino-3fluorobenzoate as an tan solid (8.2 g, 64%). H NMR (400 MHz, CD 3 OD) 6 7.56 (dd, J = 1.6 and 8.0 Hz, IH), 7.52 (dd, J = 1.9 and 12 Hz, IH), 6.76 (t, J = 8.4 Hz, IH), 3.81 (s, 3H) ppm. 19F NMR (400 MHz, CD 3 OD) 6 -139.05 (IF) ppm. ES-HRMS m/z 170.0565 (M+H calcd for CsHgFNO 2 requires 170.0612). Step 3 Preparation of methyl 3-fluoro-4- (4-hydroxy-6-methy!- 2-oxopyridin-l(2H)-yl)benzoate OH CO 2 Me A 250 mL round bottomed flask equipped with stirbar, DeanStark trap and reflux condensor was charged with the product of Step 2 (8 g, 47.3 mmol), 4-hydroxy-6-methyl-2-pyrone (12 84.6 mmol), and N-methyl-2-pyrrolidine (8 mL). The system was immersed in a 150 C oil bath for 2 hours and was then cooled to room temperature. The reaction mixture was washed with aqueous K 2 CO 3 (8.5 g, 200 mL water). The aqueous layer was washed with ethyl acetate and then was acidified to pH 4-5 with glacial HOAc. This was extracted with ethyl acetate, which was then concentrated in vacuo. The viscous oil was triturated with acetonitrile and filtered to the title compound as a tan solid (2.3 g, 17%). IH NMR (400 MHz, CD 3 OD) 19 F NMR (400 MHz, CD 3 OD) 6 -123.00 (IF) ppm. ES-HRMS m/z 278.0781 (M+H calcd for C 4 HI 3 FNO 4 requires 278.0823). Step 4 Preparation of methyl 4- [4- [(2,4-dif!uorobenzyl)oxy]- 6-methyl-2-oxopyridin-I (2H) -yl] -3-fluorobenzoate CO 2 Me A I00 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the product of Step 4 (2.3 g, 8.3 mmol) and N,N-dimethyl formamide (20 niL). 1,8diazabicyclo[5.4.0]undec-7-ene (1.4 mL, 9.1 mmol) was added followed by 2,4-difluorobenzyl bromide (1.2 mL, 9.1 mmol) . The reaction mixture was stirred at 60 C for 3 h, was poured into saturated aqueous NaHCO and was extracted with ethyl acetate. The organic layer was washed with brine and concentrated in vacuo. The solid was triturated with acetonitrile and filtered to give the title compound (2.15 g, 64%). IH NMR (400 MHz, CODED) 6 7.99 (dd, J = 1.7 and 8.4 Hz, IH), 7.93 (dd, J = 1.8 and 10.4 Hz, IH) , 7.55 (m, IH), 7.48 (t, J = 6.8 Hz, IH), 7.02 (m, 2H), 6.18 (dd, J = 1.3 and 2.76 Hz, IH), 6.02 (d, J = 2.7 Hz, IH), 5.14 (s, 2H), 3.94 (s, 3H), 1.98 (s, 3H) ppm. 9 F NMR (400 MHz, CODED) 6 -111.34 (IF), 115.97 (i F) , -122.98 (i F) ppm. ES-HRMS m/z 404.1133 (M+H calcd for C 21 HITF 3 NO 4 requires 404.1104). Step 5 Preparation of methyl 4-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-3fluorobenzoate F .Br F F.¢ CO 2 CH 3 A i00 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the product of Step 4 (2.15 g, 5.3 mmol) and N-methyl-2-pyrrolidine (15 mL) . After cooling to 0 C, a solution of N-bromo succinimide (1.03 g, 5.8 mmol) in i0 mL of N-methyl-2-pyrrolidine was added over 15 minutes. After 15 additional minutes, the reaction mixture was warmed to room temperature and was stirred for 1 hour. The mixture was then poured into saturated aqueous NaHCO 3 and extracted with ethyl acetate. The organic layer was washed with brine and concentrated in vacuo. The residue was triturated with acetonitrile and filtered to give the title compound as a white powder (1.5 g, 59%). IH NMR (400 MHz, CD 3 OD) 6 8.00 (dd, J = 2.0 and 8.4 Hz, IH), 7.95 (dd, J = 1.7 and I0 Hz, IH), 7.64 (q, J = 8.8 and 14.4 Hz, IH), 7.51 (t, J = 7.6 Hz, IH), 7.04 (t, J = 8.4 Hz, 2H), 6.66 (s, IH), 5.36 (s, 2H), 3.95 (s, 3H), 2.01 (s, 3H) ppm. 19 F NMR (400 MHz, CD OD) 6-111.50 (IF), -115.97 (i F), -123.01 (I F) ppm. ES-HRMS m/z 484.0169 (M+H calcd for C 21 HI BrF 3 NO 4 requires 484.0192). Example 605 O OH O 4-{ [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin-l(2H)-yl]methy!}benzoic acid. Preparation of 4-{ [3-chloro-4- [(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]methyl}benzoic acid. Methyl-4- { [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2-oxopyridinl(2H)-yl]methyl}benzoate (30.4 g, 70.1 mmol) was suspended in methanol (150 mL) and dioxane (150 mL). 2.5N NaOH (30.8 mL, 77.08 mmol) was added. The resulting mixture was heated to °C for 8.0 hours. The reaction was partially concentrated and the heterogenous mixture was acidified (pH 2) with IN HC1. The precipitate was collected by filtration washing with H 2 0 and diethyl ether to afford a white solid (29.2 g, 99 %). IH NMR (400 MI4z, DMSO-d 6 ) 6 7.88 (d, J = 8.3 Hz, 2H), 7.63 (app q, J = 7.9 Hz, IH), 7.31 (dr, J = 2.4, 9.9 Hz, IH), 7.18 (app d, J = 8.3 Hz, 2H) , 7.17-7.12 (m, IH), 6.60 (s, IH) , 5.35 (s, 2H), 5.27 (s, 2H), 2.28 (s, 3H). ES-HRMS m/z 420.0821 (M+H calcd for CnHITCIF 2 N0 4 requires 420.0809). Example 606 oxopyridin-1 (2H) -yl] methyl }benzamide Preparation of 4-{ [3-chloro-4- [ (2,4-difluorobenzyl)oxy] - 6-methyl-2-oxopyridin-i (2H) -yl] methyl}benzamide. 4- { [3chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridinl(2H)-yl]methyl}benzoic acid (12.0 g, 28.58 mmol) was suspended in tetrahydrofuran (i00 mL) . 2-Chloro-4,6dimethoxy-l,3,5-triazine (6.02 g, 34.3 mmol) was added followed by 4-methylmorpholine (9.43 mL, 85.74 mmol) . The resulting mixture was stirred at room temperature for 1.5 hours at which time NH 4 OH (50.0 mL) was added. The resulting mixture was stirred at room temperature for 1 hour and then partially concentrated. The precipitate was collected by filtration washing with H 2 0 and diethyl ether to provide an off-white solid (12.11 g, >i00 %). IH NMR (400 MHz, DMSO-d 6 ) 7.91 (br s, IH), 7.80 (d, J = 8.3 Hz, 2H), 7.63 (app q, J = 7.9 Hz, IH), 7.31 (dr, J = 2.6, 10.5 Hz, IH), 7.17-7.12 (m, IH) , 7.13 (app d, J = 8.3 Hz, 2H) , 6.59 (s, IH) , 5.32 (s, 2H) 5.27 (s, 2H), 2.28 (s, 3H). ES-HRMS m/z 419.0968 (M+H calcd for CnHIsCIF 2 N 2 0 requires 419.0969). Example 607 4- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6 -methyl -2oxopyridin1 (2H) -yl ] methyl } -N, N-dimethylbenzamide Preparation of 4-{[3-chloro-4-[(2,4-dif!uorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}}-N,N~dimethylbenzamide. 4-{ [3-chloro-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}benzoic acid (2.00 g, 4.76 mmol) was suspended in N,N-dimethylformamide (20 mL) . lHydroxybenzotriazole (0.773 g, 5.72 mmol) was added followed by 4-methylmorpholine (l.57mL, 14.28 mmol), dimethylamine (7.14 mL, 2.0 M in tetrahydrofuran, 14.28 mmol) and then 1-[3- (dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.28 g, 6.66 mmol). The resulting mixture was stirred at room temperature for 3 hours at which time the reaction was diluted with H O (75 mL). The reaction mixture was then extracted with ethyl acetate. The combined organic extracts were washed with saturated NaHC0 brine, dried over Na 2 S0 4 , filtered and concentrated. The resulting solid was washed with ethyl acetate to provide the title compound as a white solid (1.67 2.26 (s, 3H). ES-HRM$ m/z 447.1246(M+H calcd for C= H 22 CIF 2 N 2 0 3 requires 447.1282). Example 608 O H O 4-{ [3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}-N-(2-hydroxy-2methylpropyl)benzamide Preparation of 4-([3-chloro-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}-N-(2-hydroxy-2- methylpropyl)benzamide. 4-{ [3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}benzoic acid (2.00 g, 4.76 mmol) was suspended in N,N-dimethylformamide (i0 mL). l-Hydroxybenzotriazole (0.772 g, 5.71 mmol) was added followed by 4-methylmorpholine (l.57mL, 14.28 mmol), l-amino-2-methyl-2-propanol hydrochloride (1.49 g, 11.90 mmol) and then 1-[3- (dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.28 g, 6.66 mmol). The resulting mixture was stirred at room temperature for 2 days at which time the reaction was diluted with H 2 0 (50 mL). The reaction mixture was then extracted with ethyl acetate. The combined organic extracts were washed with saturated NaHCO 3 , brine, dried over Na 2 SO 4 , filtered and concentrated. The resulting solid was washed with diethyl ether to provide the title compound as a tan solid (2.08 g, 89%). IH NMR (400 MHz, CDCI 3 ) 6 7.72 (d, J = 8.2 Hz, 2H), 7.51 (app q, J = 7.7 Hz, 1H), 7.25-7.21 (m, IH), 7.i0 (d, J 8.2 Hz, 2H), 6.93 (app dr, J = 1.6, 8.3, 9.4 Hz, IH) , 6.876.82 (m, IH) , 6.01 (s, IH) , 5.32 (s, 2H) , 5.19 (s, 2H) , 3.42 (d, J = 5.9 Hz, 2H), 2.26 (s, 3H), 1.23 (s, 6H) . ES-HRMS m/z 491.1522 (M+H calcd for C 2 sH 26 CIF 2 N 2 0 4 requires 491.1544). Example 609 H O N- {4- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin-I (2H) -yl] benzyl } -2-hydroxyacetamide. Step i. Preparation of l-[4-(aminomethyl)phenyl]-3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methylpyridin-2 (iH)-one. F\ Example 244 (0.250 g, 0.556 mmol) was suspended in tetrahydrofuran (2.0 mL) and cooled in an ice-bath. Borane dimethyl sulfide (0.500 mL, 2.0 M in tetrahydrofuran, 1.00 mmol) was added. The resulting mixture was heated to reflux overnight and then cooled in an ice-bath. The reaction was quenched by the addition of 6.0 N HCI (5.0 mL) then washed with ethyl acetate. The aqueous layer was made alkaline with 2.5 N NaOH and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na 2 SO 4 , filtered and concentrated to provide an off-white solid (0.180 g, 74 %). IH NMR (400 MHz, CDCI 3 ) 6 7.58 (app q, J = 7.8 Hz, IH), 7.44 (app d, J = 8.2 Hz, 2H), 7.10 (d, J = 8.2 Hz, 2H), 6.95 (app dt, J = 1.5, 8.5 Hz, IH) , 6.88-6.83 (m, IH) , 6.06 (s, IH), 5.24 (s, 2H), 3.93 (s, 2H), 1.96 (s, 3H) . Step 2. Preparation of 2-({4-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-!(2H)~ yl]benzyl}amino)-2-oxoethyl. O H O O Acetoxyacetic acid (0.037 g, 0.310 mmol) was dissolved in dichloromethane (2.0 mL). l-hydroxybenzotriazole (0.021 g, 0.155 mmol) was added followed by 3-(1cyclohexylcarbodiimide)propyl-functionalized silica gel (i.00 g, 0.620 mmol, loading = 0.64 mmol/g). After stirring at room temperature for 15 minutes, l-[4-(aminomethyl)phenyl]-3-bromo4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one (Step i) (0.180 g, 0.310 mmol) in dichloromethane (2.0 mL) was added. The resulting mixture was stirred at room temperature overnight, at which time the reaction mixture wasfiltered and concentrated. Chromatography (silica gel, hexanes/ethyl acetate with 10% methanol) provided a white solid (0.130 g, Step 3. Preparation of N-{4-[3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]benzyl]-2hydroxyacetamide. 2-({4-[3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]benzyl}amino)-2-oxoethyl (Step 2) (0.130 g, 0.243 mmol) was dissolved in methanol (5 mL) and H 2 0 (i mL). K 2 C0 3 (0.055 g, 0.398 mmol) was added and the resulting mixture was stirred at room temperature for 2 hours. The mixture was then concentrated and the residue was partitioned between H 2 0 and ethyl acetate. The organic layer was removed and the aqueous layer was further extracted with ethyl acetate. The combined organic layer were washed with brine, dried over Na 2 S0 4 , filtered and concentrated to provide an off-white solid (0.i00 g, 84%). IH NMR (400 MHz, CDCI 3 ) 6 7.56 (app q, J = 7.7 Hz, IH), 7.43 (t, J = 5.8 Hz, IH), 7.33 (d, J = 8.2 Hz, 2H), 7.04 (app d, J = 8.3 Hz, 2H), 6.98-6.93 (m, IH), 6.88-6.83 (m, IH), 6.11 (s, IH), 5.24 (s, 2H), 4.41 (d, J = 6.0 Hz, 2H), 3,87 (s, 2H), 1.96 (s, 3H) . ES-HRMS m/z 493.0575 (M+H calcd for C 22 H 20 BrF 2 N 2 0 4 requires 493.0569). Example 610 3- [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl] benzamide Example 291 (2.00 g, 4.93 mmol) and 2-chloro-4,6-dimethoxy- 1,3,5-triazine (1.04 g, 5.91 mmol) were suspended in tetrahydrofuran (20 niL). 4-Methylmorpholine (1.6 mL, 14.79 mmol) was added. The resulting mixture was stirred for 1.5 hours at room temperature. NH 4 0H (I0 mL, 148.00 mmol) was added and the reaction was stirred for 0.5 hours at room temperature. H 2 0 (50 mL) and tetrahydrofuran (50 mL) were added and the organic layer was separated. The aqueous phase was extracted with ethyl acetate (75 mL) and the combined organics were washed with saturated Na 2 CO 3 (50 mL), IN HCI (50 mL), and brine (50 mL). The organic phase was dried over Na 2 S0 4 and evaporated. The resulting solid was washed with diethyl ether to give a white solid (1.96 g, 98%). IH NMR (400 MHz, DMF-d 6 ) 6 8.24 (br s, iN), 8.10 (dt, J = 1.21, 7.79 Hz, IH) , 7.90 (t, J = 1.88 Hz, IH), 7.79 (app dt, J = 6.58, 8.59 Hz, IH), 7.66 (t, J = 7.79 Hz, IH), 7.57-7.55 (m, IH), 7.46 (br s, IH), 7.33 (ddd, J = 2.55, 9.26, 11.82 Hz, IH) 7.24-7.19 (m, IH), 6.78 (s, IH), 5.44 (s, 2H), 2.04 (s, 3H). ES-HRMS m/z 405.0835 (M+H calcd for C 20 HI 6 BrF 2 N 2 0 3 requires 405.0812). Example 611 I- (4-aminobenzyl) - 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6methylpyridin-2 (IH) -one Step l: Preparation of l-tert-butyl-4-{ [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}phenylcarbamate. OTNH 4-.{ [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}benzoic acid (8.00 g, 17.23 mmol) was suspended in i:i acetonitrile:t-butanol (172 mL) . Diphenylphosphoryl azide (5.69 g, 20.68 mmol) and triethylamine (2.08 g, 20.68 mmol) were added. The reaction was heated to reflux for 1.5 hours. The reaction mixture was cooled to room temperature, concentrated and subjected to chromatography (on silica, ethyl acetate with 10% methanol/hexanes) to afford an off-white solid (6.14 g, 66%). Step 2: l-tert-butyl-4-{ [3-bromo-4-[(2,4-difiuorobenzyl)oxy]- 6-methyl-2-oxopyridin-I (2H) -yl]methyl}phenylcarbamate (Step l) (6.14 g, 11.47 retool) was suspended in 4N HCI in dioxane (5.74 mL, 22.94 mmol) . The reaction mixture was stirred at room temperature for 1 hour then diluted with diethyl ether. The precipitate was collected by filtration and washed with diethyl ether (3 x 30 mL) to afford a tan solid (3.45 g, 69%). IH NMR (400 MHz, DMF-d 6 ) 6 7.64 (app dt, J = 6.58, 8.59 Hz, IH) , 7.31 (ddd, J = 2.55, 9.53, 10.61 Hz, IH) 7.29-7.12 (m, 5H) , 6.56 (s, IH) , 5.28 (s, 2H), 5.27 (s, 2H) , 2.28 (s, 3H) . ES-HRMS m/z 435.0516 (M+H calcd for C 20 HIaBrF 2 N 2 0 2 requires 435.0514). Example 612 NH 2 1 - ( 3 - aminobenzyl ) - 3 -bromo4 - [ (2,4 - di f i uorobenzyl ) oxy] - 6 - methylpyridin2 (IH) - one By following the method for Example 611 and substituting 3- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridinl(2H)-yl]methyl}benzoic acid for 4-{ [3-bromo-4- [ (2,4di f luorobenzyl ) oxy] - 6 -methyl - 2 - oxopyridin1 (2H) - yl]methyl}benzoic acid , the title compound was prepared (2.65 IH), 5.30 (s, 2H) , 5.27 (s, 2H) , 2.29 (s, 3H) . ES-HRMS m/z 435.0513 (M+H calcd for C 0 H:eBI'F 2 N O 2 requires 435.0514). Example 613 O O NH N- (4- { [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin1 (2H) -yl ] methyl } phenyl) acetamide To a reaction vessel (borosilicate culture tube) was added Example 611 (0.300 g, 0.689 mmol) and dichloromethane (3.0 mL) . A stock solution of N-methylmorpholine (0.30 M, 3.0 mL) was added and the parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for i0 minutes. Acetyl chloride (0.074 mL, 1.033 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature for 1.5 hours. At this time the reaction was diluted with dichloromethane (15 mL) and treated with approximately 2.1 g of polyamine resin (2.63 mmol/g) and approximately 3.8 g of methylisocyanate functionalized polystyrene (I.I0 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature overnight. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were rinsed with dichloromethane (2 x i0 mL). The filtrate was evaporated by blowing N 2 over the vial to afford a white solid (0.135 g, 41%). H NMR (400 MHz, DMF-d 6 ) 6 7.75 (app dr, J = 6.58, 8.59 Hz, IH), 7.63 (d, J = 8.59 Hz, IH), 7.30 (ddd, J = 2.55, 9.53, 10.61 Hz, IH) , 7.22-7.14 (m, 3H), 6.60 (s, IH), 5.37 (s, 4H), 2.40 (s, 3H), 2.06 (s, 3H) . ES-HRMS m/z 477.0600 (M+H calcd for C 22 H IBrF 2 N 2 0 3 requires 477.0620) . Preparation of Examples 614-616 O O <NH R By following the method for Example 613 and replacing acetyl chloride with the appropriate acid chloride or sulfamoyl chloride, the compounds of Examples 614-616 are prepared. The deprotection of the protected intermediate was accomplished with IM K 2 CO in methano! to afford the title compound. Compound % M+H ES-HRMS R MF No. Yield Requires m/z Example 617 N- (3-{ [3-bromo-4- [ (2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin1 (2H) -yl] methyl }phenyl) acetamide To a reaction vessel (borosilicate culture tube) was added Example 612 (0.300 g, 0.689 mmol) and dichloromethane (3.0 mL). A stock solution of N-methylmorpholine (0.30 M, 3.0 mL) was added and the parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for i0 minutes. Acetyl chloride (0.074 mL, 1.033 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature for 1.5 hours. At this time the reaction was diluted with dichloromethane (15 mL) and treated with approximately 2.1 g of polyamine resin (2.63 mmol/g) and approximately 3.8 g of methylisocyanate functionalized polystyrene (i.i0 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature overnight. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were rinsed with dichloromethane (2 x I0 mL). The filtrate was evaporated by blowing N 2 over the vial to afford a white solid (0.167 g, 51%). IH NMR (400 MHz, DMF-d ) 6 7.77 (app dr, J = 6.58, 8.59 Hz, IH), 7.69 (d, J = 8.32 Hz, IH), 7.41 (br s, IH), 7.34-7.17 (m, 3H), 6.88 (d, J = 7.65 Hz, IH), 6.63 (s, 1H), 5.39 (s, 3H), 5.38 (s, 2H), 2.40 (s, 3H}, 2.06 (s, 3H) . ES-HRMS m/z 477.0620 (M+H calcd for C 22 H BrF 2 N 2 0 3 requires 477.0620). Preparation of Example 618-620 F\ O O H By following the method for Example 617 and replacing acetyl chloride with the appropriate acid chloride or sulfamoyl chloride, the compounds of Examples 618-620 are prepared. The deprotection of the protected intermediate was accomplished with IM K 2 CO] in methanol to afford the title compound. Compound % M+H ES-HRMS R MF No. Yield Requires m/z Example 621 N- (4-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin1 (2H) -yl ] methyl }benzyl) -N' -methylurea Preparation of (4-{ [3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6_methy!-20 x 0 pyridin-l(2H)-yl]methyl}benzyl)-N'-methylurea. EXAMPLE 159 (150 mg, 0.33 mmol) was dissolved in N,Ndimethylacetamide 5 mL) and cooled to 0° C. 4-Nitrophenyl chloroformate (I00 mg, 0.5 mmol) was added, followed by N,Ndiisopropylethylamine (0.15 mL, 0.85 mmol) and the reaction was stirred at 0° C for 5 minutes. N-Methylamine (0.5 mL, 1.0 mmol, 2M in tetrahydrofuran) was added and the reaction was allowed to reach ambient temperature and stirred for 1 hour. The reaction was then diluted with tetrahydrofuran (40 mL) and polyamine resin (1.3 g, 2.81 mmol/g) and methylisocyanate functionalized polystyrene (i g, 1.38 mmol/g) were added. The mixture was shaken for 16 hours at ambient temperature, filtered, and the resulting filtrate concentrated to an oil that was triturated with ether. The resulting white solid was collected, washed with ether, and dried (87 mg, 52%). IH NMR (400 MHz, CDHOD) 6 7.61 (app q, J = 8.4 Hz, IH); 7.24 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 7.02 (app t, J = 8.4 Hz, 2 H) , 6.47 (s, IH) , 5.39 (s, 2H) , 5.28 (s, 2H) , 4.26 (s, 2H) ; 2.68 (s, 3H) ; 2.34 (s, 3H) . ES-HRMS m/z 506.0862 (M+H calcd for C 23 H 23 BrF 2 N 3 0 3 requires 506.0885). Example 622 O H N- (4- { [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2oxopyridin1 (2H) -yl] methyl }benzyl) -N' - (2-hydroxy-2methylpropyl)urea Preparation of N-(4-{ [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}benzyl)-N'-(2-hydroxy-2-methylpropyl)urea. EXAMPLE 159 (300 mg, 0.67 mmol) was dissolved in N,N-dimethylacetamide (5 mL) and cooled to 0° C. 4-Nitrophenyl chloroformate (200 mg, 1.0 mmol) was added, followed by N,N-diisopropylethylamine (0.3 mL, 1.7 mmol) and the reaction was stirred at 0° C for minutes. 3-Amino-2-methyl-2-propanol (248 mg, 2.0 mmol) was added and the reaction was allowed to reach ambient temperature and stirred for 3 h. The reaction was then diluted with tetrahydrofuran (40 mL) and polyamine resin (1.3 g, 2.81 mmol/g) and methylisocyanate functionalized polystyrene (i g, 1.38 mmol/g) were added. The mixture was shaken for 16 hours at ambient temperature, filtered, and the resulting filtrate concentrated to an oil that was triturated with ether. The resulting white solid was purified by chromatography (silica gel, hexane/ethyl acetate/methanol) followed by reversed phase chromatography (C 18 , 0.1% aqueous trifluoroacetic acid/acetonitrile) to yield an off-white solid (43 mg, 11%). IH 1.14 (s, 6H) . ES-HRMS m/z C 2 H 29 BrF 2 N 3 0 4 requires 564.1304) 564.1279 (M+H calcd for Example 623 Fx. H N- (4- { [3-bromo-4- [ (2,4-difluorobenzyl] oxy] - 6-methyl2- oxopyridin-l(2H)-yl]methyl}benzyl)piperidine-l-carboxamide By following the general method for Example 622 and substituting piperidine (170 mg, 2.0 mmol) for 3-amino-2methyl-2-propanol the title compound was prepared and purified by chromatography (silica gel, hexane/ethyl acetate/methanol) yielding an oil that was triturated with ether to afford a white solid (107 mg, 28%). IH NMR (400 MHz, CDCI 3 ) 6 7.56 (app q, J = 8.0 Hz, IH) ; 7.23 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 7.02 (app t, J = 8.0 Hz, 2H), 6.81-6.88 (m, IH), 5.97 (s, IH) , 5.32 (s, 2H) , 5.19 (s, 2H) ; 4.37 (s, 2H) ; 3.34-3.28 (m, 4H) ; 2.29 (s, 3H) ; 1.68-1.50 (m, 6H) . ES-HRMS m/z 560.1365 (M+H calcd for C 2 vH 29 BrF 2 N 3 0 3 requires 560.1355) . Example 624 " <¢o N- (4- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl ] methyl } benzyl ) morphol ine4 - carboxamide By following the general method for Example 622 and substituting morpholine (175 mg, 2.0 mmol) for 3-amino-2methyl-2-propanol the title compound was prepared and pu -ified by chromatography (silica gel, hexane/ethyl acetate/methanol) followed by reversed phase chromatography (C 1 a, 0.1% aqueous trifluoroacetic acid/acetonitrile) to yield an off-white solid (51 rag, 13%). H NMR (400 MHz, CDCI 3 ) 6 7.55 (app q, J = 8.0 Hz, IH) ; 7.17 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.0 Hz, 2H) , 6.94(app dt, J = 2.4, 8.0 Hz, 2H), 6.82-6.87 (m, IH), 6.02 (s, IH) , 5.27 (s, 2H) , 5.19 (s, 2H) ; 4.33 (s, 2H) ; 3.65-3.62 (m, 4H) ; 3.34-3.36 (m, 4H) ; 2.28 (s, 3H) . ES-HRMS m/z 562.1152 (M+H calcd for C 2 H 2 vBrF 2 N 3 0 4 requires 562.1148). Example 625 O H L.,.../N H N-(4-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}benzyl)piperazine-l-carboxamide hydrochloride By following the general method for Example 622 and substituting l-Boc-piperazine (372 mg, 2.0 mmol) for 3-amino2-methyl-2-propanol the title compound was prepared from its N-t-butoxycarbonyl protected intermediate that was purified by chromatography (silica gel, hexane/ethyl acetate/methanol). Deprotection was accomplished with 4N HCI in dioxane to afford the title compound as its hydrochloride salt (78 mg, 19%). IH 3.62 (m, 4H) ; 3.21-3.17 (m, 4H) ; 2.35 (s, 3H) . ES-HRMS mlz 561.1318 (M+H calcd for C 2 H sBrF 2 N 4 0] requires 561.1307). Example 626 OH H H N-(4-{ [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}benzyl)-N'-(2-hydroxyethyl)urea By following the general method for Example 622 and substituting ethanolamine (121 mg, 2.0 mmol) for 3-amino-2methyl-2-propanol the title compound was prepared and purified by chromatography (silica gel, hexane/ethyl acetate/methanol) to yield an off-white solid (130 mg, 36%). H NMR (400 MHz, CDCI ) 6 7.54 (app q, J = 7.6 Hz, IH); 7.13 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.96-6.92 (m, IH) ; 6.83-6.88 (m, IH), 6.09 (s, IH), 5.26 (s, 2H), 5.21 (s, 2H); 4.24 (s, 2H) ; 3.56 (t, J = 4.8 Hz, 2H); 3.21 (t, J = 4.8 Hz, 2H) ; 2.31 (s, 3H) . ES-HRMS m/z 536. 0948 (M+H calcd for C 24 H 2 sBrF 2 N O 4 requires 536.0991). Example 627 N' - (4- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-2oxopyridin1 (2H) -yl ] methyl } benzyl ) -N, N-dimethylurea By following the general method for Example 622 and substituting N, N-dimethylamine (I. 0 mL, 2.0 mmol, 2M in tetrahydrofuran) for 3-amino-2-methyl-2-propanol the title compound was prepared and purified by chromatography (silica gel, hexane/ethyl acetate/methanol) yielding an oil that was triturated with ether to afford a white solid (65 rag, 19%). H NMR (400 MHz, CDCI ) 6 7.56 (app q, J = 8.0 Hz, IH); 7.22 (d, J = 8.0 Hz, 2H) , 7.10 (d, J = 8.0 Hz, 2H) , 6.93 (app dt, J = 2.0, 8.0 Hz, IH) ; 6.87-6.81 (m, IH) ; 5.97 (s, IH) , 5.31 (s, 2H) , 5.19 (s, 2H) ; 4.36 Is, 2H) ; 2.89 (s, 6H) ; 2.28 (s, 3H) . ES-HRMS m/z 520. 1072 (M+H calcd for C 24 H 2 sBrF 2 N 3 0 3 requires 520.1042) . Example 628 H N-(4-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}benzyl]-4-hydroxypiperidine-lcarboxamide By following the general method for Example 622 and substituting 4-Hydroxypiperidine (202 mg, 2.0 mmol) for 3amino-2-methyl-2-propanol the title compound was prepared and purified by chromatography (silica gel, hexane/ethyl acetate/methanol) yielding an oil that was triturated with ether to afford a white solid (41 mg, 11%). IH N-MR (400 MHz, 2.28 (s, 3H) ; 1.84-1.81 (m, 2H) ; 1.47-1.44 (m, 2H) . ES-HRMS m/z 576.1348 (M+H calcd for C 27 H 29 BrF 2 N 3 0 4 requires 576.1304). Example 629 4-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]methyl}-N,N-dimethylbenzenesulfonamide Step I: Preparation of 4-Bromomethyl-N,Ndimethylbenzenesulfonamide O II "N/ i 4-(Bromomethyl)benzenesulfonyl chloride (5.0 g, 18.6 mmol) was dissolved in tetrahydrofuran. N,N-dimethylamine (7.7 mL, 15.5 mmol, 2M in tetrahydrofuran) and and N,Ndiisopropylethylamine (3.5 mL, 20.1 mmol) were added, and the reaction was allowed to stir at ambient temperature for 2 hours. The reaction was concentrated to an oil that was partitioned between water and ethyl acetate and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over Na 2 SO and filtered. The resulting filtrate was concentrated to an oil which deposited needles that were a mixture of the title compound and 4-chloromethyl N,N-dimethylbenzenesulfonamide The resulting needles were collected and dried .(2.3 g, 44 %). ES-MS m/z 534 (M+H) and Step 2: Preparation of 4-{ [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-i(2H)-yl]methyl}- N,N-dimethy!benzenesulfonamide 3-bromo-4-(2,4difluorophenoxy)-6-methylpyridin-2(1H)-one (300 mg, 0.91 mmol) was suspended in 1,4-dioxane (50 mL). 4-(Bromomethyl)-N,Ndimethylbenzenesulfonamide ( from stepl) (300 mg, 1.09 mmol) was added followed by sodium hydride (45 mg, 1.09 mmol, 60% in mineral oil). The reaction was heated to 80"C and stirred for 16 hours after which more sodium hydride (45 mg, 1.09 mmol, 60% in mineral oil) and sodium iodide (150 mg, 1.0 mmol) were added. The reaction was allowed to stir at 80'C for 4 hours more. The reaction was then filtered through Celite and the filtrate was concentrated to an oil that was purified by chromatography (silica gel, hexane/ethyl acetate) followed by reversed phase chromatography (C 18 , 0.1% aqueous trifluoroacetic acid/acetonitrile) to yield an off-white solid (41 mg, 8%). IH NMR (400 MHz, CDCI 3 ) 6 7.71(d, J = 8.4 Hz, 2H) ; 7.57 (app q, J = 7.6 Hz, IH) ; 7.29 (d, J = 8.0 Hz, 2H) ; 6.95 (app dt, J = 2.0, 8.0 Hz, IH), 6.88-6.83 (m, IH) ; 6.05 (s, IH), 5.42 (s, 2H), 5.22 (s, 2H) ; 2.69 (s, 6H); 2.29 (s, 3H) . ES-HRMS m/z 527.0439 (M+H calcd for C 22 H 22 Br 2 F 2 N 2 0 4 S requires 527.0446). Example 630 o H Br 4- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl] methyl } -N- (2-hydroxyethyl) benzenesulfonamide Step I: Preparation of 4-Bromomethyl-N-(2hydroxyethyl)benzenesulfonamide 4-(Sromomethyl)benzenesulfonyl chloride (5.0 g, 18.6 mmol) was dissolved in tetrahydrofuran. Ethanolamine (i.I mL, 18.6 mmo!) and and N,N-diisopropylethylamine (3.9 mL, 22.3 mmol) were added, and the reaction was allowed to stir at ambient temperature for 30 minutes. The reaction was concentrated to an oil that was partitioned between water and ethyl acetate and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over Na 2 SO 4 , and filtered. The resulting filtrate was concentrated to an oil that was a mixture of the title compound and 4chloromethyl N-(2-hydroxyethyl)benzenesulfonamide. The resulting oil was dried in vacuo (3.7 g, 68 %). ES-MS m/z 250 (M+H) and 294 (M+H) . Step 2 : Preparation of 4- { [3-bromo-4- [ (2,4difluorobenzyl ) oxy] - 6-methyl - 2 -oxopyridin~ 1 (2H) - yl ] methyl } -N- ( 2 - hydroxyet hyl ) benzenesul fonamide. The title compound was prepared essentially according to the procedure described in Step 2 of Example 629, using 4Bromomethyl-N- (2-hydroxyethyl) benzenesulfonamide ( from step I). IH NMR (400 MHz, CDCI 3 ) 8 7.81 (d, J = 8.4 Hz, 2H); 7.61 (app q, J = 7.6 Hz, IH) ; 7.30 (d, J = 8.4 Hz, 2H) ; 6.95 (app t, J = 8.4 Hz, 2H) , 6.53 (s, IH) , 5.49 (s, 2H) , 5.30 (s, 2H) ; 3.50 (t, J = 6.0 Hz, 2H) ; 2.92 (t, J = 6.0 Hz, 2H) ; 2.36 (s, 3H) . ES-HRMS m/z 543.0453 (M+H calcd for C 22 HnBr 2 F 2 N 2 OsS requires 543.0395) . Example 631 F O 4-{ [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-exopyridinl(2H)-yl]methyl}-N-(2-hydroxy-2methylpropyl)benzenesulfonamide Step I: Preparation of 4-Bromomethyl-N-(2-hydroxy-2methylpropyl) benzenesulfonamide O OH Br-. 4- (Bromomethyl)benzenesulfonyl chloride (2.0 g, 7.3 mmol) was dissolved in tetrahydrofuran. 3-Amino-2-methyl-2-propanol (l.O g, 8 mmol) and and N,N-diisopropylethylamine (1.5 mL, 8.8 mmol) were added, and the reaction was allowed to stir at ambient temperature for 30 minutes. The reaction was concentrated to an oil that was partitioned between water and ethyl acetate and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over Na 2 SO 4 , and filtered. The resulting filtrate was concentrated to an oil that was a mixture of the title compound and 4chloromethyl-N-(2-hydroxy-2-methylpropyl) benzenesulfonamide. The resulting oil was dried in vacuo 1.9 g, 81%). Step 2: Preparation of 4-{ [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]methyl}-N- (2-hydroxy-2-methylpropyl)benzenesulfonamide The title compound was prepared essentially according to the procedure described in Step 2 of Example 629, using 4Bromomethyl-N-(2-hydroxy-2-methylpropyl) benzenesulfonamide ( from step i) . IH NMR (400 MHz, CDC! 3 ) 6 7.78 (d, J = 8.4 Hz, 2H) ; 7.56 (app q, J = 7.6 Hz, IH) ; 7.26 (d, J = 8.4 H=) ; 6.95 (app t, J = 8.4 Hz, IH), 6.86-6.83 (m, IH) ; 6.07 (s, IH), 5.41 (s, 2H) , 5.22 (s, 2H) ; 4.98 (t, J = 6.4 Hz, IH) ; 2.84 (d, J 6.4 Hz, 2H) ; 2.29 (s, 3H) ; 1.21 (s, 6H) . ES-HRMS m/z 571.0684 (M÷H calcd for C 24 H 2 Br 2 F 2 N=0 5 S requires 571.0708). Example 632 F 3-Chloro-4-(2,4-difluorobenzyloxy)-6-methyl-l-(iH-pyrazol-3ylmethyl)-iH-pyridin-2-one Step i. Preparation of 4-Hydroxy-6-methyl-IH-pyridin-2-one. OH 4-Hydroxy-6-methyl-pryan-2-one (25.8 g, 0.2 mol) was dissolved in 180 ml of concentrated ammonium hydroxide. The reaction was heated at refluxed for 4 hours. The reaction was cooled to room temperature and evaporated on a rotary evaporator to a quarter of the original volume. The resulting solid was filtered, washed with cold water, hexanes, and dried in a vacuum oven overnight to give a white solid (25 g, 98%): IH NMR Step 2. Preparation of 3-Chloro-4-hydroxy-6-meth¥1-1Hpyridin-2-one. OH .CI H 4-Hydroxy-6-methyl-iH-pyridin-2-one (25g, 0.2 tool) and Nchlor-osuccinimide (29.4 g, 0.22 mol) were dissolved in 200 of acetic acid. The reaction was heated at 115 °C for 6 hours. The reaction was cooled to room temperature, the solid was filtered, and washed with acetic acid and hexanes. The solid was dried in a vacuum oven overnight to give a white solid (19.2 g, 60%): iH N-MR (300 MHz, DMSO-d ) 6 11.46 (br s, IH), 11.04 (s, IH), 5.79 (s, IH) , 2.09 (s, 3H) . Step 3. Preparation of 3-Chloro-4-(2,4-difluorobenzyloxy)-6methyl-IH-pyridin-2-one. H 3-Chloro-4-hydroxy-6-methyl-IH-pyridin-2-one (19.2 g, 0.12 mol) and DBU (19.9 mL, 0.13 mol) were dissolved in 70 mL of NMP. 2,4-Difluorobenzylbromide (17 mL, 0.13 mol) was added dropwise and the reaction was heated at 80 °C for 6 hours. The reaction was cooled to room temperature, the solid was filtered, and washed with NMP and hexanes. The solid was dried in a vacuum oven overnight to give a white solid (4.4 g, 13%): IH NMR (300 MHz, DMSO-d 6 ) 6 11.88 (br s, IH), 7.63 (app q, J = 9 Hz, IH), 7.33 (app t, J = i0 Hz, IH), 7.16 (app t, J = 9 Hz, IH), 6.37 (s, IH) , 5.24 (s, 2H), 2.20 (s, 3H) . Step 4. Preparation of 3-Methylpyrazole-l-carboxylic acid tert-but¥1 ester. oNBoc N 3-Methyl-IH-pyrazole (5.3 g, 65 mmol), DMAP (0.79 g, 6.5 mmol), and di-tert-butyl dicarbonate (2.8 g, 13 mmol) were at room temperature in 90 mL of CH 3 CN for 1 hour.. The reaction was evaporated on a rotary evaporator, and the resulting solid dissolved in EtOAc, washed with 1 N HCI, water and brine, dried (MgSO 4 ), filtered, and evaporated on a rotary evaporator to give a light yellow oil (11.4 g, 96%): IH NMR (300 MHz, CDCI 3) 6 7.96 (d, J = 2.7 Hz, IH), 6.17 (d, J = 2.7 Hz, IH), 2.32 (s, 3H), 1.63 (s, 9H). Step 5. Preparation of 3-Bromomethylpyrazole-l-carboxylic acid tert-butyl ester. 3-Methylpyrazole-l-carboxylic acid tert-butyl ester (6.0 g, 33 mmol), N-bromosuccinimide (i.0 g, 5.6 mmol) and benzoyl peroxide (50 mg) were dissolved in 20 mL of carbon tetrachloride. The reaction was heated at reflux for 16 h. The reaction was cooled to room temperature, filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:4 Et0Ac/hexanes) gave a light yellow oil (4.5 g, 53%): IH NMR (300 MHz, CDCI ) 6 8.03 (d, J = 2.6 Hz, IH), 6.47 (d, J = 2.6 Hz, IH), 4.48 (s, 2H), 1.64 (s, 9H) . Step 6. Preparation of 3-[3-Chloro-4-(2,4-difluorobenzyloxy)- 6-methyl-2-oxo-2H-pyridin-l-ylmethyl]pyrazole-l-carboxylic acid tert-butyl ester. NBoc O 3- [3-Chloro-4- (2,4-difluorobenzyloxy)-6-methyl-2-oxo-2Hpyridin-l-ylmethyl]pyrazole-l-carboxylic acid tert-butyl ester was prepared by a procedure similar to the one described for Example 401 gave a yellow solid (1.4 g, 39%) : IH NMR (300 MHz, CDCI 3) 7.537.49 (m, 2H), 6.976.81 (m, 2H), 6.35 (d, J = 2.0 Hz, IH), 6.01 (s, IH) , 5.32 (s, 2H) , 5.26 (s, 2H) , 2.52 (s, 3H), 1.62 (s, 9H). Step 7. Preparation of the title compound Example 632 3-[3Chloro-4- (2,4-difluorobenzyloxy)-6-methyl-2-oxo-2H-pyridin-lylmethyl]pyrazole-l-carboxylic acid tert-butyl ester (0.16 g, 0.34 mmol) was heated to 140 °C for 16 h. The reaction mixture was cooled to room temperature. Recrystallization from methylene chloride/hexanes provided an off-white solid Example 633 H O 3-Chloro-4-(2,4-difluorobenzyloxy)-6-methyl-l-(2,3-dihydro-iHindol-5-ylmethyl)-iH-pyridin-2-one Step i. Preparation of 5-[3-Chloro-4-(2,4-difluorobenzyloxy)- 6-methyl-2-oxo-2H-pyridin-l-ylmethyl]indole-l-carbamic acid tert-butyl ester Bo¢ O 5- [3-Chloro-4- (2,4-difluorobenzyloxy) -2-oxo-2H-pyridin-lylmethyl]indole-l-carbamic acid tert-butyl ester was prepared by a procedure similar to the one described for Example 632 as an off-white solid (2.5 g, 61%): IH NMR (300 MHz, DMSO-d 6 ) 6 8.00 (d, J = 8.5 Hz, IH), 7.70 - 7.62 (m, 2H), 7.39 - 7.32 (m, 2H), 7.217.13 (m, 2H), 6.70 (d, J = 3.8 Hz, IH), 6.66 (s, IH), 5.40 (s, 2H), 5.29 (s, 2H), 2.33 (s, 3H), 1.62 (s, 9H) . Step 2. Preparation of 3-Chloro-4-(2,4-difluorobenzyloxy)-6methyl-l-(iH-indol-5-ylmethyl)-iH-pyridin-2-one pyridin-l-ylmethyl]indole-l-carbamic acid tert-butyl ester (l.08g, 2.1 retool) dissolved in 40 mL of DMSO was stirred at 120 °C for 20 hours. The reaction was cooled to room temperature, diluted with water, and washed 5 times with ethyl acetate. The combined organics were washed 1 time with brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure, iH NMR (300 MHz, DMSO-d ) 6 ii.I (br s, IH), 7.67 (d, J = 6.7 Hz, IH), 7.36 - 7.32 (m, 2H), 7.23 (s, IH), 7.18 (d, J = 2.3 Hz, IH), 6.93 (dd, J = 8.4, 1.2 Hz, IH), 6.57 (s, IH), 6.38 (s, IH), 5.37 (s, 2H), 5.29 (s, 2H), 2.35 (s, 3H) . Step 3. 3-Chloro-4 - (2,4 -difluorobenzyloxy) - 6 -methyl-l- (IH- indol-5-ylmethyl)-iH-pyridin-2-one (, from Step 2) (1.7 g, 4.1 mmol) was stirred in 26 mL of acetic acid and NaCNBH 3 (0.27 g, 4.3 mmol) was added portionwise. The reaction was stirred for 1 hour. The reaction was diluted water, and washed 5 times with ethyl acetate. The combined organics were washed 1 time with brine, dried (MgS0 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 100% EtOAc) gave a white solid (1.2 g, 71%) : IH NMR Example 634 5_[ 3_Chl 0 r 0-4-(2,4-difluorobenzyloxy)-6-methyl-2-oxo-2Hpyridin-l-ylme hyl]-l,3-dihydro-indol-2-one Step I. Preparation of 5-[3-Chloro-4-(2,4-difluorobenzyloxy)- 6_methyl_20 x 0-2H-pyridin-l-ylmethyl]-3,3-dibromo-iH-indol-2one. F H O O Br 3-Chl 0 r 0-4-(2,4-diflu 0 r 0 benzyl 0 xy)-6-methyl-l-(iH-indol-5ylmethyl)-IH-pyridin-2-one (0.45 mg, I.I mmol) (example 633, step 2) was suspended in Ii mL of tert-butanol and pyridinium bromide perbromide (1.04 g, 3.3 mmol) was added portionwise. The reaction was stirred for 16 hours. The reaction was diluted with water, and washed 4 tires with ethyl acetate. The combined organics were washed 1 time with brine, dried (MgS0 4), filtered, and concentrated under reduced pressure. Trituration with methylene chloride gave an off-white solid Step 2. 5- [3-Chloro-4- (2,4-difluorobenzyloxy)-6-methyl-2-oxo- 2H-pyridin-l-ylmethyl] -3,3-dibromo-iH-indol-2-one (0.2 g, 0.34 mmol) was suspended in 5 mL of acetic acid, and zinc metal (0.22 g, 3.4 mmol) was added. The reaction was stirred for 48 hours. The reaction was diluted with water, and washed 2 times with ethyl acetate. The combined organics were washed 1 time with brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 100% EtOAc) gave a white solid (0.12 g, 82%): IH NMR (300 MHz, DMSO-d 6 ) 6 10.37 (br s, IH), 7.65 (app q, J = 6.9 Hz, IH), 7.34 (dr, J = 8.2, 2.5 Hz, IH), 7.18 (dr, J = 7.1, 1.9, IH), 6.98 (br s, 2H), 6.77 (d, J = 8.4 Hz, IH), 6.57 (s, IH) , 5.28 (s, 2H), 5.23 (s, 2H), 3.44 (s, 2H), 2.34 (s, 3H) . Example 635 F N.....SO 2 Me I N- [ (5- { [3-Bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl ] methyl } pyrazin2 -yl ) methyl ] -Nmethylmethanesulfonamide To a suspension of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-l-({5- [(methylamino)methyl]pyrazin-2-yl}methyl)pyridin2(IH)-one (0.16 g, 0.34 mmol) in acetonitrile at 0 °C was added triethylamine (0.043 g, 0.42 mmol), followed by the addition of methane sulfonylchloride (0.047 g, 0.41 mmol) and stirred at room temperature for 1 h under argon atmosphere. The solvents were removed in vacuo and he residue was triturated with water and filtered. It was washed with water an, acetonitrile and dried in vacuo to afford 0.II g of material. IH NMR (CDaOD/ 400 M'Hz) 6 8.62 (s, IH), 8.55 (s, IH), 7.61 (m, IH), 7.0 (m, 2H), 6.53 (s, IH), 5.47 (s, 2H), 5.29 (s, 2H) , 4.49 (s, 2H), 2.95 (s, 3H), 2.85 (s, 3H) , and 2.55 (s, 3H) ; 19F NMR(CD 3 OD/ 400 MHz) -lll.70(m) and -116.07 (m) ; ES-HRMS m/z 543.0515(M+H calcd for C 2 H 22 BrF 2 N O 4 S requires 543.0508). Example 636 F Methyl (5-{[3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyi-2oxopyridin-l(2H)-yl]methyl}pyrazin-2yl)methyl(methyl)carbamate To a cold (5 °C) solution of 3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-l-((5- [(methylamino)methyl]pyrazin-2-yl}methyl)pyridin-2(iH)-one (0.20 g, 0.4 mmol) in DMF (2.0 ml), was added methylchloroformate (0.049 g, 0.52 mmol), followed by the addition of triethylamine (0.072 g, 0.71 mmol). The mixture was stirred at 5 °C for 30 min and at room temperature for an additional 30 min and concentrated in vacuo The residue was partitioned between water (5.0 mL) and EtOAc (10.0 mL). The organic extract was washed with water, dried (Na 2 SO 4 ), and concentrated to dryness. The resulting material was purified by reverse-phase H?LC using 10 -90 % CH 3 CN/ Water gradient (60 min) at a flow rate of 70 mL/min. The appropriate fractions (m/z = 523 M+H ) were combined and freeze dried to give a white powder. This was partitioned between 5% NaHC0 3 I10 mL) and EtOAc (15 mL). The organic layer was washed with water, dried (Na 2 SO 4 ), and concentrated to dryness to afford the title compound (0.12 g, 53%) as a white powder: IH NMR (CD 3 OD/ 400 MHz) 6 8.59 (s, IH), 8.41(m, IH) , 7.60 (m, IH) , 7.05 (m, 2H), 6.52 (s, IH>, 5.45 (s, 2H) 5.29 (s, 2H), 4.58 (s, 2H), 3.69 and 3.64 (s, 3H), 2.97 (s, 3H), 2.85 (s, 3H), and 2.55 (s, 3H) ; 19F NMR(CD 3 OD/ 400 MHz -iii.69(m) and -116.09 (m) ; ESHRMS m/z 523. 0775 (M+H calcd for C 22 H 22 BrF 2 N 4 0 requires 523.0787) . Example 637 < o N- [ (5- [ [3-Bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin - 1 ( 2 H ) -yl ] methyl } pyraz in2 -yl ) methyl ] - 2 - hydroxyN, 2 dimethylpropanamide To a cold (5 °C) solution of 3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-l-({5- [(methylamino)methyl]pyrazin-2-yl}methyl)pyridin-2(iH)-one (0.24 g, 0.52 mmol) in DMF (2.0 ml), was added 2acetoxyisobutyryl chloride (0.093g, 0.56 mmoi), followed by the addition of triethylamine (0.072 g, 0.71 mmol) . The mixture was stirred at room temperature for an additional 2 h and concentrated in vacuo The residue was partitioned between water (5.0 mL) and EtOAc (15.0 mL). The EtOAc extract was washed with water, dried (Na 2 S0 4 ), and concentrated to dryness. The resulting material (0.2 g) was stirred with IM. LiOH (0.5 mL, MeOH,/Water l:iv/v) at room temperature for 3h, cooled, acidified with trifluoroacetic acid and the product was purified by reverse-phase HPLC using i0 -90 % CH 3 CN/ Water gradient (60 min) at a flow rate of 70 mL/min. The appropriate fractions (m/z = 551 M+H ) were combined and freeze dried to give a white powder. This was partitioned between 5% NaHCO 3 (I0 mL) and EtoAc (15 mL) . The organic layer was washed with water, dried (Na 2 SO 4 ), and concentrated to dryness to afford the title compound 0.075 g) as a white powder: :H NMR (CD OD/ 400 MHz) 6 8.59 (s IH), 8.41(br, IH), 7.60 (m, 2H), 7.01 (m, 2H), 6.52 (s, IH) 5.45 (s, 2h), 5.29 (s, 2H), Example 638 'F N /N 0<' 0 H 5-{ [3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]methyl}-N-(2-hydroxy-2-methylpropyl)pyrazine-2carboxamide To a solution of 5-{[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}pyrazine-2-carboxylic acid (0.42 g, 0.9 mmol) in DMF (3.0 mL) was added isobutylchloroformate (0.126 g, 0.13 mmol) followed by the addition of N-methylmorpholine (0.ii g, i.i mmol ) and stirred at -i0 °C, under argon atmosphere. After min, added a solution of i,i dimethyl-2-aminoethanol hydrochloride (0.135g, !.I mmol) in DMF (2.0 mL) containing N- methylmorpholine (0.Ii g, i.I mmol) . The mixture was stirred at room temperature for 1 h, and concentrated to dryness in vacuo. The resulting residue was purified by reverse-phase HPLC using i0 -90 % CH 3 CN/ Water gradient (60 min) at a flow rate of 70 mL/min. The appropriate fractions (m/z = 537 M+H were combined and freeze dried to give a white powder. This was partitioned between 5% NaHCO 3 (I0 mL) and EtOAc (15 mL) . The organic layer was washed with water, dried (Na 2 SO 4 ) , and concentrated to dryness to afford the title compound (0.35 g, 75%) as a white powder: IH NMR (CD OD/ 400 MHz) 69.1 (d, IH, J = 1.6 Hz), 8.71 (d, IH, J = 1.6 Hz) , 7.61 (m IH) , 7.02 (m, 2H), 6.54 (s, IH), 5.54 (s, 2H), 5.30 (s, 2h) . 3.30 (s, 2h), 2.55 (s, 3H), and 1.21 (s, 6H) ; 29F NMR(CD 3 OD/ 400 MHz) -iii.67(m) and -116.05 (m) ; ES-HRMS m/z 537.0948 (M+H calcd for C 23 H 24 BrF 2 N 4 0 4 requires 537.0943). Example 639 difluorobenzyl)oxy]-6-methylpyridin-2(!H)-one trif!uoroacetate A mixture of 5-{ [3-bromo-4-[(2,4-difluorobenzy!)oxy]-6-methyl2-oxopyridin-l(2H)-yl]methyl}pyrazine-2-carboxylic acid (0.70g, 1.5 mmol) diphenylphosphoryl azide (0.51 g, 1.8 mmol) in dimethvlacetamide (15.0 mLl and t-butanol (5.0 mL) containing triethylamine (0.18 g, 1.8 mmol) was heated at 90 °C for 6 h under argon atmosphere. The reaction mixture was cooled, filtered the precipitate. It was washed with acetonitrile and dried to obtain 0.22 g of the unreacted acid. The con%bilned filtrate and the washings were concentrated in vacuo and the resulting material was purified by reverse-phase HPLC using I0 -90 % CH 3 CN/ Water gradient (60 min) at a flow rate of 70 naL/min. The appropriate fractions (m/z = 437 M+H ) were combined and freeze dried to give the title compound (0.21g, 37%) as a white powder: iH N]4R (DMSO-d 6 / 400 MHz) 67.88 (d, IH, J = 1.2 Hz) , 7.75 (d, IH, J = 1.2 Hz) , 7.61 (m IH), 7.34 (m, IH), 7.18 (m, IH), 6.49 (s, IH), 5.25 (s, 2H), 5.10 (s, 2H), and 2.49 (s, 3H); 19F NMR(CD 3 OD/ 400 MHz) -Iii.72 (m) and -116.11 (m) ; ES-HRMS m/z 437.0402 (M+H calcd for C 18 HI BrF 2 N 4 0 2 requires 437.0419). Example 640 %<r F CF 3 COOH 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-[(3-methyl1,2,4-triazin-6-yl)methyl]pyridin-2(iH)-one trifluoroacetate Step i: Preparation of (2-methylpyrimidin-5-yl)methanol trifluoroacetate N/OH CFaCOOH To solution of methyl 2-methylpyrimidinecarboxylate (2.6 g, 17.1 mmol) in THF was added dropwise diisobutylaluminumhydride (39.5 mL, IM solution in THF) and stirred at -20 °C under argon atmosphere for 1.5 h, and at room temperature for 2 h. The reaction was quenched by the addition of powdered sodiumsulphate decahydrate (25 g), added THF (25 mL) and stirred at room temperature for lb. This mixture was allowed to stand in the refrigerator overnight and filtered through a celite pad. The precipitate was thoroughly with warm THF (i00 mL) containing 10% ethanol. The combined washings and the filtrate were concentrated to afford ayellow syrup, which was purified by reverse-phase HPLC using i0 -90 % CH CN/ Water gradient (60 min) at a flow rate of 70 mL/min. The appropriate fractions (m/z = 125 M+H) were combined and lyophilized to give the title compound (0.67 g, 32%) as its trifluoroacetate salt: IH NMR (CD 3 OD/ 400 MHz) 68.65 (s, 2H ) 4.62 (s, 2H), and 2.66 (s, 3H) ; ES-HRMS m/z 125.0678 (M+H calcd for C HgN 2 0 requires 125.0709). Step 2: Preparation of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-l-[(3-methyl-l,2,4-triazin-6-yl)methyl]pyridin-2(IH)- one trifluoroacetate To a solution of (2-methylpyrimidin-5-yl)methanol trif!uoroacetate (0.9 g, 3.76 mmo!) in dichloromethane (i0 mL) at 0 °C, was added triethylamine (0.95 g, 9.41 mmol), followed by the addition of methanesulfonyl chloride (0.59 g, 5.17 mmol) and stirred at 0 °C for 1 h. After stirring for 1 h at room temperature, additional triethylamine ( 0.22 g) and methanesulfonyl chloride (0.15 g)were added and the mixture was stirred at room temperature for another hour under argon atmosphere. The reaction was quenched by the addition of cold water (15 mL) and stirred for 15 min. The organic layer was washed with water, followed by 5% sod. bicarbonate (2 x mL), water, and dried (Na 2 S0 4 ). After the removal of the solvent under reduced pressure, the residue was dried in a desiccator under vacuum for 4 h. This material was suspended in THF (i0 mL) and DMF (5.0 mL), added 3-bromo-4-(2,4difluorophenoxy)-6-methylpyridin-2(iH)-one (0.5 g, 1.52 mmol) and NaH (0.04 g) . The resulting mixture was heated at 65 °C for 16 h under argon atmosphere. The solvents were distilled under vacuum and the residue was purified by reverse-phase HPLC using I0 -90 % CH 3 CN/ Water gradient (60 min) at a flow rate of 70 mL/min. The appropriate fractions (m/z = 436 M÷H) were combined and freeze dried to give the title compound (0.045 g,) as its trifluoroacetate salt: IH NMR (CD OD/ 400 MHz) 88.58 (s, 2H) 7.61 (m, IH), 7.01 (m, 2H), 6.53 (s, IH), 5.37 (s, 2h), 5.29 (s, 2H), 2.65 (s, 3H), and 2.46 (s, 3H) ; 19F NMR(CD 3 OD/ 400 MHz) -111.62 (m), and -116.08 (m) ; ES-HRMS m/z 436. 0433 (M+H calcd for C 19 HITBrF 2 N 3 0 2 requires 436.0467). Example 641 3-Bromo-4- [ (2,4-difluorobenzyl)oxy]-lIiH-indazol-5-yl) -6methylpyridin2 (1H) -one Step I: Preparation of 4-hydroxy-l-(iH-indazol-5-yl)-6methylpyridin-2(iH)-one O N / A mixture of 4hydoxy-6-methyl-2-pyrone (3.75 g, 0.029 mol) and 5-aminoindazole (4.0 g, 0.03 mol) in water (70 ml) was heated at 90 °C under argon for 1 h. The mixture was cooled, decanted the supernatant and residue was triturated with ethanol, cooled and filtered the solid. It was washed with cold ethanol, and dried. IH NMR (CD 3 OD/ 400 MHz) 68.11 (s, IH), 7.64 (m, 2H), 7.18 (d, IH, J = 2.0 Hz ), 7.16 (d, IH, J = 2.0 Hz) 6.07 (m, IH) , 5.81 (d, IH, J = 2.8 Hz) , and 1.94 (s, 3H); ES-HRMS m/z 242.0962(M+H calcd for C 13 HI 2 N 3 0 2 requires 242.0924) . Step 2: A mixture of 4-hydroxy-l-(IH-indazol-5-yl)-6methylpyridin-2(iH)-one (0.2g, 0.83 mmol), Nbromosuccinmide (0.15 g, 0.84 mmol) in dichloromethane (4.0 mL) and acetic acid (i.0 mL) was stirred at room temperature under argon atmosphere for 2.5 h. After the removal of the solvents, the residue was dried in vacuo for 4 h in a desiccator. It was then suspended in DMF (3.0 mL), potassium carbonate (0.1g), and 2,4 difluorobenzyl bromide were added and mixture was stirred at room temperature for 3 h. DMF was distilled in vacuo and the residue was purified by reverse-phase HPLC using i0 -90 % CH 3 CN/ Water gradient (60 min) at a flow rate of mL/min. The appropriate fractions (m/z = 537 M+H ) were combined and freeze dried to give a white powder. This was partitioned between 5% NaHCO 3 (!0 mL) and EtOAc (15 mL). The organic layer was washed with water, dried (Na 2 SO 4 ), and concentrated to dryness to afford the title compound (0.075 g) as a white powder: IH NMR (CD 3 OD/ 400 MHz) 88.13 (s, IH ), 7.68 (m, 3H) , 7.20 (2d, IH, J = 1.2 Hz), 7.05 (m, 2H), 6.61 (s, IH) , 5.35 (s, 2H) , and 2.05 (s, 3H) ; 19F NMR(CD OD/ 400 MHz) - 111.62 (m) and -116.02 (m) ; ES-HRMS m/z 446.0305(M+H calcd for C 0 HIsBrF 2 N 3 0 2 requires 446.0310). Example 642 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-(iH-indazol-6-yl)-6methylpyridin-2(iH)-one Step i: Preparation of 4-hydroxy-l-(IH-indazol-6-yl)-6methylpyridin-2(IH)-one The title compound was prepared by a similar procedure described for 4-hydroxyl-l- (iH-indazol-5-yl) -6-methylpyridin2 (IH)-one. Yield = 12%; IH NMR (CD 3 OD/ 400 MHz) 6 8.12 (s, IH) 7.90 (d, IH, J = 8.0 Hz), 7.42 (s, IH), 6.94 (d, IH, J = 8.8 Hz) 6.08 (br s, IH), 5.81 (d, IH, J = 2.4 Hz), and 1.96 (s, 3H) ; ES-HRMS m/z 242.0946(M+H calcd for CI 3 HI 2 N O 2 requires 242.0924) . Step 2 : The title was prepared by a similar procedure described for Bromo-4- [ (2,4-difluorobenzyl)oxy]-l- (iH-indazol-5-yl)-6methylpyridin-2 (IH)-one. IH NMR (CD OD/ 400 MHz) 6 8.14 (s, IH) 7.93 (d, IH, J = 8.4Hz), 7.61 (m IH) , 7.46 (s, IH) , 7,04 (m, 2H), 6.98 (m, IH) 6.62 (s, IH), 5.36 (s, 2H), and 2.06 (s, 3H) ; 19F NMR(CD 3 OD/ 400 MHz) -iii.62 (m) and -116.03 (m) ; ESHRMS m/z 446. 0302 (M+H calcd for C 13 HI 2 N 3 0 2 requires 446.0310). Example 643 0 Br iH NH OCH 3 methyl 2-{ [ (3-bromo-6-methyl-l-{2-methyl-5- [(methylamino)carbonyl]phenyl}-2-oxo-l,2-dihydropyridin-4yl)oxy]methyl}-5-fluorobenzylcarbamate Step I: Preparation of methyl 3-[4-[(2-cyano-4fluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4methy!benzoate o o< OMe N TO a cooled (0°C) solution of 2-(bromomethyl)-5fluorobenzonitrile (4.31 g, 20.1 mmol) and methyl 3-(4hydroxy-6-methyl-2-oxopyridin-l{2H)-yl)-4-methylbenzoate (5.00 g, 18.3 mmol) in DMF (20 mL) was added K 2 C0 3 (3.00 g, 22.0 mmol) . The reaction was allowed to warm to RT and stirred overnight. Additional 2-(bromomethyl)-5-fluorobenzonitrile (0.39 g, 1.83 mmol) and K 2 C0 3 (0.25 g, 1.83 mmol) were added and the reaction heated at 60°C for 2h. Solvent removed by distillation. Reaction neutralized with 5% citric acid (50 mL). Organic products were extracted in DCM (3 x 25 mL), dried over Na 2 S0 4 , filtered, and concentrated to a thick dark brown oil. Purified by silica gel flash column chromatography using EtOAc as the eluent to give the product as a brown solid, dried in vacuo (6.18 g, 76%). :H NMR (CD 3 OD/ 400MHz) 68.03 (m, IH), 7.76 (m, 2H), 7.66 (m, IH), 7.52 (m, 2H), 6.24 (s, IH), 6.09 (s, IH), 5.27 (s, 2H), 3.89 (s, 3H), 2.12 (s, 3H), 1.90 (s, 3H) . ESHRMS m/z 407.1408 (M+H calculated for C 23 H 20 FN 2 0 4 requires 407.1402). Step 2: Preparation of methyl 3-[4-{[2-(aminomethyl)-4fluorobenzyl]oxy}-6-methyl-2-oxopyridin-l(2H)-yl]-4methylbenzoate trifluoroacetate To a cooled (0°C) solution of methyl 3-[4-[(2-cyano-4fluorobenzyl) oxy] - 6-methyl-2-oxopyridin-I (2H) -yl] -4- methylbenzoate ( from Step i) (0.510 g, 1.25 mmol) in THF (5 mL) was added dropwise BH 3 THF (2.51 mL, 2.51 retool). The reaction was then stirred at RT for 2.5h. Reaction cooled (0°C), quenched by the slow addition of MeOH, concentrated, and purified by preparatory HPLC. The product was isolated by freeze-drying and evaporation of the solvent to give a white solid, dried in vacuo (0.39 g, 76%) . IH NMR (CD 3 OD/ 400MHz) 68.04 (m, IH), 7.75 (s, IH), 7.63 (m, IH) , 7.55 (d, IH, J = Hz), 7.32 (m, IH) , 7.24 (m, IH), 6.25 (s, IH), 6.12 (s, IH), 5.23 (s, 2H), 4.25 (s, 2H) , 3.90 (s, 3H), 2.11 (s, 3H), 1.90 (s, 3H). ESHRMS m/z 411.1691 (M+H calculated for C 2 ]H 24 FN 2 0 4 requires 411. 1715) . Step 3: Preparation of methyl 3- [4- [(4-fluoro-2- { [ (methoxycarbonyl) amino] methyl } benzyl ) oxy] - 6 -methyl - 2 - oxopyridin1 (2H) -yl ] - 4 -methylbenzoate To a cooled (0°C) solution of methyl 3-[4-{ [2- (aminomethyl) -4fluorobenzyl] oxy} -6-methyl-2-oxopyridin1 (2H) yl]-4-methylben'zoate trifluoroacetate ( from Step 2) (0.50 g, 0.95 mmol) in DMA (4 mL) was added 4-methylmorpholine (0.21 mL, 1.9 mmol) and methy! chloroformate (0.08 mL, 1.0 mmol). Reaction was stirred at RT for lb. Solvent removed by distillation. Crude product purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHCO 3 (30 mL) and extracted in DCM (3 x 25 mL) . The organic extracts were dried over Na 2 S0 4 , filtered, and concentrated to a white solid, dried in vacuo (0.36 g, 81%). IH NMR (CD 3 OD/ 400MHz) 68.03 (m, IH), 7.77 (s, IH), 7.53 (d, IH, J = 7.6 Hz), 7.47 (m, IH), 7.12 (m, IH), 7.03 (m, IH), 6.21 (s, IH), 6.08 (s, IH), 5.18 (s, 2H), 4.38 (s, 2H), 3.89 (s, 3H), 3.65 (s, 3H), 2.12 (s, 3H), 1.89 (s, 3}{). ESHRMS m/z 469.1767 (M+H calculated for C 2 sH 2 FN 2 0 requires 469.1769). Step 4: Preparation of 3- [4-[(4-fluoro-2- {[(methoxycarbonyl)amino]methyl}benzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-4-methylbenzoic acid To methyl 3- [4- [(4-fluoro-2- { [ (methoxycarbonyl) amino] methyl } benzyl) oxy] - 6-methyl2- oxopyridin-l(2H)-yl]-4-methylbenzoate ( from Steo 3) (0.17 0.36 mmol) was added 1.5 N NaOH solution in I:i MeOH:water (0.39 mL, 0.59 mmol). The reaction mixture was stirred at for 2.5h. The solution was cooled (0°C), neutralized by the slow addition of 5% citric acid, and organic products extracted in DCM. A white solid suspended in the organic layer was filtered, washed with DCM and water, dried in vacuo, and found to be the desired product (0.090 g, 55%). IH NMR (CD 3 OD/ 400MHz) 68.03 (m, IH), 7.75 (s, IH), 7.52 (d, IH, J 8.0 Hz), 7.47 (m, IH), 7.12 (m, IH), 7.03 (m, IH), 6.21 (s, IH), 6.08 (s, IH), 5.18 (s, 2H) , 4.38 (s, 2H), 3.65 (s, 3H), 2.12 (s, 3H), 1.90 (s, 3H) . ESHRMS m/z 455.1632 (M+H calculated for C 24 H 24 FN 2 0 6 requires 455.1613) . Step 5: Preparation of 3- [3-bromo-4- [ (4-fluoro-2- { [ (methoxycarbonyl) amino] methyl } benzyl ) oxy] - 6 -methyl-2 - oxopyridin-l(2H)-yl]-4-methylbenzoic acid. NBS (0.6£ g, 3.85 retool) was added to a solution of 3-[4- [ (4fluoro-2- ( [ (methoxycarbonyl) amino] methyl }benzyl) oxy] -6methyl-2-oxopyridin-l(2H)-yl]-4-methylbenzoic acid ( from Step 4) (1.75 g, 3.85 retool) in DCM (45 mL). After 1.5h, solvent removed on rotary evaporator. Solid dissolved in EtOAc and hexane added, resulting in a solid precipitate. Solid filtered. Solid subsequently dissolved in DCM and washed with water. Organic layer dried over Na 2 S0 4 , filtered, and concentrated. Pale yellow solid dried in vacuo (1.47 g, 72%). IH NMR (CD OD/ 400MHz) 68.04 (m, IH), 7.77 (s, IH), 7.54 (m, 2H), 7.13 (m, IH), 7.05 (m, IH), 6.68 (s, IH), 5.40 (s, 2H), 4.44 (s, 2H), 3.64 (s, 3H), 2.09 (s, 3H), 1.99 (s, 3H). ESHRMS m/z 533.0700 and 535.0677 (M+H calculated for C 24 H 23 BrFN 2 0 requires 533.0718 and 535.0701). Step 6: Preparation of the title compound . To a cooled (-10°C) solution of 3-[3-bromo-4-[(4-fluoro-2- {[(methoxycarbonyl)amino]methyl}benzyl)oxy]-6-methyl-2- oxopyridin-l(2H)-yl]-4-methylbenzoic acid (0.07 g, 0.13 mmol) in DMF (2.0 mL) was added isobutyl chloroformate (0.02 mL, 0.16 mmol) and 4-methylmorpholine (0.02 mL, 0.16 mmol). After 15min, 2.0M methylamine in THF (0.01 mL, 0.20 mmol) was added. Solvent removed by distillation after 30min. Crude product purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHC0 3 (30 mL) and extracted in DCM (3 x 25 mL). The organic extracts were dried over Na 2 SO 4 , filtered, concentrated, and dried in vacuo to give a white foam, (0.061 g, 86%). ZH NMR (CD 3 OD/ 400MHz) 67.85 (m, IH), 7.54 (m, 3H), 7.14 (m, IH), 7.05 (m, IH), 6.68 (s, IH), 5.40 (s, 2H) , 4.43 (s, 2H) , 3.64 (s, 3}{), 2.89 (s, 3H) , 2.08 (s, 3H) , 1.99 (s, 3H) . ES}{RMS m/z 546.0987 and 548.1018 (M+H calculated for C 2 sH 2 BrFN 3 Os requires 546.1034 and 548.1018). Example 644 0 ,Br F o< HO OCH 3 methyl 2-({[3-bromo-l-(5-{[(2-hydroxyethyl)amino]carbonyl}-2methylphenyl)-6-methyl-2-oxo-l,2-dihydropyridin-4yl]oxy}methyl)-5-fluorobenzylcarbamate The title compound was prepared using a procedure similar to that used in the preparation of Example 643. XH NMR (CD 3 OD/ 400MHz) 67.88 (m, IH), 7.61 (s, IH), 7.53 (m, 2H), 7.13 (m, IH), 7.04 (m, IH), 6.68 (s, IH), 5.41 (s, 2H), 4.43 (s, 2H), 3.68 (t, 2H, J = 5.6 Hz), 3.64 (s, 3H), 3.48 (t, 2H, J = 5.6Hz) , 2.08 (s, 3H), 2.00 (s, 3H) . ESHRMS m/z 576.1101 and 578.1072 (M+H calculated for C 2 H 28 BrFN 3 0 6 requires 576.1140 and Example 645 0 Br o, t ) HO OCH 3 methyl 2-({ [3-bromo-l-(5-{ [(2-hydroxy-2methylpropyl)amino]carbonyl}-2-methylphenyl)-6-methyl-2-oxo1,2-dihydropyridin-4-yl]oxy}methyl -5-fluorobenzylcarbamate The title compound was prepared using a procedure similar to that used in the preparation of Example 643. iH NMR (CD 3 OD/ 400MHz) 67.89 (m, IH), 7.63 (s, IH), 7.54 (m, 2H), 7.13 (m, IH), 7.04 (m, IH), 6.69 (s, IH), 5.41 (s, 2H), 4.43 (s, 2H), 3.64 (s, 3H), 3.38 (s, 2H), 2.09 (s, 3H), 2.01 (d, 6H, J = 3.2 Hz), 1.21 (s, 3H). ESHRMS m/z 604.1412 and 606.1418 (M+H calculated for C 28 H 32 BrFN 3 0 requires 604.1453 and 606.1438). Example 646 methyl 2_({[3-bromo-l-(5-{ [(2-methoxyethyl)amino]carbonyl}-2methylphenyl)-6-methyl-2-oxo-l,2-dihydropyridin-4yl]oxy}methyl)-5-fluorobenzylcarbamate The title compound was prepared using a procedure similar to that used in the preparation of Example 643. ZH NMR (CD 3 OD/ 400MHz) 67.87 (m, IH), 7.59 (s, IH), 7.53 (m, 2H) , 7.14 (m, IH), 7.05 (m, IH), 6.68 (s, 1H), 5.41 (s, 2H), 4.44 (s, 2H), 3.64 (s, 3H) , 3.54 (s, 4H), 3.35 (s, 3H) , 2.08 (s, 3H), 2.00 (s, 3H). ESHRMS m/z 590.1267 and 592.1219 (M+H calculated for C 2 vH 30 BrFN 3 0 6 requires 590.1297 and 592.1281). Example 647 methyl 2-[({l-[5-(aminocarbonyl)-2-methylphenyl]-3-bromo-6methyl-2-oxo-l,2-dihydropyridin-4-yl}oxy)methyl]-5fluorobenzylcarbamate The title compound was prepared using a procedure similar to that used in the preparation of Example 643. IH NMR (CDsOD/ 400MHz) 67.91 (m, IH), 7.64 (s, IH) , 7.54 (m, 2H) , 7.14 (m, IH), 7.05 (m, !H), 6.68 (s, IH), 5.40 (s, 2H), 4.44 (s, 2H), 3.64 (s, 3H), 2.09 (s, 3H), 2.00 (s, 3H) . ESHRMS m/z 532.0836 and 534.0787 (M+H calculated for C 24 H 24 BrFN 3 Os requires 532.0878 and 534.0861). Example 648 F 0 CI ' 0 F NH o< NH N-[2-({[3-chloro-l-(2,6-difluorophenyl)-6-methyl-2-oxo-l,2dihydropyridin-4-yl]oxy}methyl)-5-fluorobenzyl]-N'-phenylurea To a cooled (0°C) solution of 4-{ [2-(aminomethyl)-4fluorobenzyl]oxy}-3-chloro-l-(2,6-difluorophenyl)-6methylpyridin-2(iH)-one trifluoroacetate (0.25 g, 0.48 mmol) in DMA (2.0 mL) was added 4-methylmorpholine (0.06 mL, 0.53 mmol) and phenyl isocyanate (0.06 mL, 0.53 mmol). The reaction was stirred at RT for 1.5h. Solvent distilled and crude product purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHCO 3 (30 mL) and extracted in DCM (3 x 25 mL) . The organic extracts were dried over Na 2 SO filtered, and concentrated to a white solid, dried in vacuo (0.18 g, 71%). :H NMR (CD]OD/ 400MHz) 67.60 (m, IH), 7.54 (m, !H) , 7.33 (d, 2H, J = 7.6 Hz), 7.22 (m, 5H) , 7.06 (m, IH) , 6.95 (t, IH, J = 7.2 Hz) , 6.73 (s, IH) , 5.44 (s, 2H) , 4.53 (s, 2H) , 2.07 (s, 3H) . ESHRMS m/z 528.1304 (M+H calculated for C 2 vH 22 CIF 3 N 3 0 3 requires 528.1296). Example 649 F F NH o< O thien-3-ylmethyl 2-({ [3-chloro-l-(2,6-difluorophenyl)-6methyl-2-oxo-l,2-dihydropyridin-4-yl]oxy}methyl)-5fluorobenzylcarbamate To a cooled (0°C) solution of 4-{[2-(aminomethyl)-4fluorobenzyl]oxy}-3-chloro-l-(2,6-difluorophenyl)-6methylpyridin-2(iH}-one trifluoroacetate (0.26 g, 0.50 mmol) and I, l-carbonyldiimidazole (0.I0 g, 0.60 mmol) in DMA (2.0 mL) was added 4-me hylmorpholine (0.06 mL, 0.55 mmol). After lh at RT, 3-thiophenemethanol (0.09 mL, 0.99 mmol) was added. No product was observed after 2h at RT. NaH (0.01 g, 0.50 mmol) was added and the reaction stirred at 60°C. Reaction was complete after 20min. The reaction mixture was cooled (0°C) and acetic acid added to quench the reaction. Solvent removed by distillation. Crude product purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHCO (30 mL) and extracted in DCM (3 x 25 mL). The organic extracts were dried over Na 2 SO 4 , filtered, and concentrated to a white foam, dried in vacuo (0.20 g, 73%). IH NMR (CD 3 OD/ 400MHz) 67.61 (m, IH), 7.52 (m, IH), 7.34 (s, 2H), 7.23 (t, 3H, J = 8.4 Hz) , 7.10 (m, 2H) , 6.71 (s, IH) , 5.40 (s, 2H) , 5.07 (s, 2H) , 4.43 (s, 2H) , 2.10 (s, 3H) . ESHRMS m/z 549.0858 (M+H calculated for C 26 H 21 CIF 3 N 2 0 4 S requires 549.0857). Example 650 F iH NH o< OHt ethy! 2-{[(3-bromo-6-methyl-l-{2-methyl-5- [(methylamino)carbonyl]phenyl}-2-oxo-l,2-dihydropyridin-4yl)oxy]methyl}-5-fluorobenzylcarbamate Step I: Preparation of methyl 3- [4- [(2- { [ ( ethoxycarbonyl ) amino] methyl } - 4 - f luorobenzyl ) oxy] - 6 -methyl - 2-oxopyridin1 (2H) -yl] -4-methylbenzoate. I NH OEt Prepared using a procedure similar to that used in the preparation of methyl 3- [4- [ (4-fluoro-2- { [ (methoxycarbonyl) amino] methyl }benzyl) oxy] - 6-methyl-2oxopyridin-l(2H) -yl]-4-methylbenzoate. IH NMR (CD 3 OD/ 400MHz) 68.03 (m, IH), 7.76 (s, IH), 7.53 (d, IH, J = 8.0 Hz), 7.47 (m, IH) , 7.12 (m, IH) , 7.03 (m, IH) , 6.21 (s, IH) , 6.08 (s, IH) , 5.18 (s, 2H), 4.38 (s, 2H), 4.08 (q, 2H, J = 6.8 Hz) , 3.89 (s, 3H), 2.12 (s, 3H), 1.89 (s, 3H), 1.23 (t, 3H, J = 6.8 Hz) . ESHRMS m/z 483.1900 (M+H calculated for C 26 H 28 FN 2 0 6 requires 483.1926). Step 2: Preparation of 3-[4-[(2- {[(ethoxycarbonyl)amino]methyl}-4-fluorobenzyl)oxy]-6-methyl2-oxopyridin-l(2H)-yl]-4-methylbenzoic acid . Prepared using a procedure similar Lo that used in the preparation of 3- [4- [ (4-fluoro-2- { [ (methoxycarbonyl) amino] methyl }benzyl) oxy] -6-methyl-2- oxopyridin-l(2H)-yl]-4-methylbenzoic acid. IH NMR (CD 3 OD/ 400MHz) 68.03 (m, IH), 7.74 (s, IH), 7.48 (m, 2H), 7.11 (m, IH) , 7.03 (m, IH), 6.21 (s, IH), 6.08 (s, IH), 5.18 (s, 2H), 4.38 (s, 2H) , 4.08 (q, 2H, J = 7.2 Hz), 2.11 (s, 3H) , 1.90 (s, 3H), 1.23 (t, 3H, J = 7.2 Hz) . ESHRMS m/z 469.1738 (M+H calculated for C 2 sH 26 FN 2 0 6 requires 469.1769). Step 3: Preparation of 3- [3-bromo-4-[(2- {[(ethoxycarbonyl)amino]methyl}-4-fluorobenzyl)oxy]-6-methyl2-oxopyridin-l(2H)-yl]-4-methylbenzoic acid. OH NH 0< OEI Prepared using a procedure similar to that used in Step of the synthesis of Example 643. IH NMR (CD OD/ 400MHz) 68.04 m/z 547.0842 and 549.0818 (M+H calculated for C 2 sH sBrFN 2 0 6 requires 547.0875 and 549.0858). Step 4 : Prepared using a procedure similar to that used in the preparation of Example 643. IH NMR (CD OD/ 400MHz) 57.85 (m, IH) , 7.54 (m, 3H), 7.13 (m, IH) , 7.04 (m, IH) , 6.68 (s, IH) , 5.40 (s, 2H), 4.43 (s, 2H), 4.07 (q, 2H), 2.89 (s, 3H), 2.08 (s, 3H), 1.99 (s, 3H), 1.23 (t, 3H, J = 7.2 Hz) . ESHRMS m/z 560.1215 and 562.1193 (M+H calculated for C 26 H 28 BrFN Os requires 560.1191 and 562.1175). Example 651 .F NH l NH o< NH I 3- [3-bromo-4-{ [2-({ [ (cyclopropylamino)carbonyl] amino}methyl)- 4 - f luorobenzyl ] oxy } - 6 -methyl - 2 -oxopyridin1 (2H) -yl ] -N, 4 - dimethylbenzamide Step i: Preparation of methy! 3-[4-{[2- ({[(cyclopropylamino)carbony!]amino}methyl)-4fiuoroben=yl]oxy}-6-methyl-2-oxopyridin-!(2H)-yl]-4methylbenzoate NH NH To a cooled (0°C solution of methyl 3-[4-{ [2- (aminomethyl) -4 -fluorobenzyl] oxy} -6-methyl-2-oxopyridin1 (2H) yl]-4-methylbenzoate trifluoroacetate () (1.13 g, 2.16 mmol and l,l-carbonyldiimidazole (0.42 g, 2.59 mmol) in DMA (8.0 mL) was added 4-methylmorpholine (0.36 mL, 3.2 mmol) . Reaction was stirred at RT for 2h. DMA removed by distillation. Crude product purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHCO 3 (30 mL) and extracted in DCM (3 x 25 mL). The organlc extracts were dried over Na 2 S0 4 , filtered, concentrated, and dried in vacuo (0.78 g, 73%) . IH NMR (CD 3 OD/ 400MHz) 68.03 (m, IH), 7.76 (s, IH), 7.53 (d, IH, J = 8.0 Hz), 7.46 (m, IH), 7.12 (m, IH) , 7.01 (m, IH), 6.22 (s, IH) , 6.08 (s, IH), 5.19 (s, 2H) , 4.44 (s, 2H) , 3.89 (s, 3H), 2.48 (m, IH) , 2.12 (s, 3H), 1.89 (s, 3H), 0.70 (m, 2H), 0.47 (m, 2H) . ESHRMS m/z 494.2076 (M+H calculated for C 27 H 29 FN Os requires 494.2086). Step 2: Preparation of 3- [4-{ [2- ({[(cyclopropylamino)carbonyl]amino}methyl)-4fluorobenzyl]oxy}-6-methyl-2-oxopyridin-l(2H)-¥!]-4methylbenzoic acid o< NH Prepared using a procedure similar to that used in the preparation of 3- [4- [ (4-fluoro-2- { [ (methoxycarbonyl) amino] methyl }benzyl ) oxy] - 6-methyl-2oxopyridin-I (2H)-yl]-4-methylbenzoic acid. H NMR (CD 3 OD/ 400MHz) 68.02 (m, IH), 7.74 (s, IH), 7.48 (m, 2H), 7.12 (m, IH), 7.01 (m, IH), 6.22 (s, IH), 6.08 (s, IH), 5.19 (s, 2H), 4.44 (s, 2H), 2.48 (m, IH), 2.11 (s, 3H), 1.90 (s, 3H), 0.69 (m, 2H), 0.47 (m, 2H). ESHRMS m/z 480.1921 (M+H calculated for C 2 H 2 FN 3 0 5 requires 480.1929). Step 3: Preparation of 3-[3-bromo-4-{ [2- ({ [(cyclopropylamino)carbonyl]amino}methyl)-4fluorobenzyl]oxy}-6-methyl-2-oxopyridin-l(2H)-yl]-4methylbenzoic acid Prepared using a procedure similar to that used in Step of the synthesis of Example 643. IH NMR (DMSO-d / 400MHz) 67.92 (m, IH) , 7.67 (s, IH), 7.54 (m, 2H) , 7.12 (m, 2H), 6.71 (s, IH), 5.37 (s, 2H), 4.31 (d, 2H, J = 6.4 Hz) , 2.40 (m, IH), 2.00 (s, 3H) , 1.88 (s, 3H), 0.56 (m, 2H) , 0.33 (m, 2H) . ESHRMS m/z 558.0988 and 560.0981 (M+H calculated for C 26 H 26 BrFN 3 Os requires 558. 1034 and 560. 1018) . Step 4: Prepared using a procedure similar to that used in the preparation of Example 643. IH NMR (CD 3 OD/ 400MHz) 67.85 (m, IH), 7.54 (m, 3H), 7.14 (m, IH), 7.03 (m, IH), 6.69 (s, IH), 5.41 (s, 2H), 4.48 (s, 2H), 2.89 (s, 3H) , 2.48 (m, IH), 2.08 (s, 3H), 1.99 (s, 2H) 0.70 (m, 2H), 0.47 (m, 2H) . ESHRMS m/z 571.1348 and 573.1355 (M+H calculated for C 2 vH 29 BrFN 4 0 4 requires Example 652 F 0 ,Br F NH 3- [3-bromo-4- { [2- ( { [ (cyclopropylamino) carbonyl] amino}methy!) 4fluorobenzyl ] oxy} - 6-methyl2-oxopyridin1 (2H) -yl] -4- methylbenzoic acid Step I: Preparation of ethyl (5-fluoro-2methylphenoxy)acetate. CH 0 To a solution of 5-fluoro-2-methylphenol (I.00 g, 7.93 mmol) and ethylbromoacetate (1.59 g, 9.51 mmol) in DMF (15 mL) was added K 2 CO (I.i0 g, 7.93 mmol). After 30min at RT, DMF was removed by distillation. The crude product was washed with 5% citric acid (30 mL) and water (30 mL), extracted in DCM (3 x 20 mL), dried over Na 2 S0 4 , filtered, concentrated, and dried in vacuo. Desired product obtained as yellow oil (1.30 Hz), 2.18 (s, 3H), 1.27 (t, 3H, J = 7.2 Hz). ESHRMS m/z 212.0847 (M+H calculated for C:!HI FO 3 requires 212.0849). Step 2: Preparation of ethyl [2-(bromomethyl)-5fluorophenoxy]acetate. F A solution of ethyl (5-fluoro-2-methylphenoxy)acetate (from Step i) (0.65 g, 3.06 mmol), NBS (0.65 g, 3.68 mmol), and benzoyl peroxide (0.05 g, 0.21 mmol) in CC14 (7.0 mL] were refluxed at 90°C for 2.5h. Additional NBS (0.16 g, 0.92 mmol) added, and reaction continued overnight. Solid filtered and filtrate concentrated onto silica gel. Purified by flash column chromatography using hexane and 2.5% EtOAc/hexane as eluent. Product obtained as yellow liquid (0.27 g, 30%). IH NMR (CD 3 OD/ 400MHz) 67.37 (m, IH), 6.69 (m, 2H), 4.80 (s, 2H), 4.60 (s, 2H), 4.23 (q, 2H, J = 7.2 Hz), 1.27 (t, 3H, J = 7.2 Hz) . Step 3: Preparation of ethyl [2-({ [3-bromo-l-(2,6difluorophenyl)-6-methyl-2-oxo-l,2-dihydropyridin-4yl]oxy}methyl)-5-fluorophenoxy]acetate. To a solution of ethyl [2-(bromomethyl)-5fluorophenoxy]acetate (from Step 2) (0.59 g, 2.03 mmol) and 3bromo-l- (2,6-difluorophenyl] -4-hydroxy6-methylpyridin-2 (IH) - one (0.61 g, 1.93 mmol) in DMF (3.0 mL) was added K 2 C0 3 (0.34 g, 2.43 mmol) . After 2h at RT, DMF was removed by distillation. The crude product was washed with 5% citric acid, extracted in DCM, dried over Na 2 SO 4 , filtered, and concentrated onto silica gel. Purified by flash column chromatography using 50% EtOAc/hexane as the eluent. Obtained product as a pale yellow solid (0.45 g, 42%). IH NMR (CD 3 OD/ 400MHz) 67.21 (q, 3H, J = 8.4 Hz), 6.80 (m, 2H), 6.69 (s, IH), 6.15 (s, IH), 5.40 (s, 2H), 4.84 (s, 2H), 4.23 (q, 2H, J = 6.8 Hz), 2.08 (s, 3H), 1.26 (t, 3H, J = 6.8 Hz). ESHRMS m/z 526.0446 and 528.0414 (M+H calculated for C 2 H 20 BrF 3 NOs requires 526.0471 and 528.0454). Step 4: Preparation of [2-({[3-bromo-l-(2,6-difluorophenyl)- 6-methyl-2-oxo-l,2-dihydropyridin-4-yl]oxy}methyl)-5fluorophenoxy]acetic acid. A solution of ethyl [2-({ [3-bromo-l-(2,6-difluorophenyl -6methyl-2-oxo-l,2-dihydropyridin-4-yl]oxy}methyl)-5fluorophenoxy]acetate (from Step 3) (0.62 g, 1.18 mmol) 1.5 NaOH solution in i:i MeOH:water (1.2 mL, 1.77 mmol), and THF (1.2 mL) were refluxed at 60°C for lh. The solution was concentrated on a rotary evaporator, cooled, and 5% citric acid added. The solid precipitate was filtered and dried vacuo. Product obtained as a pale yellow solid (0.35 g, 60%). IH N-MR (CODING 400MHz) 57.59 (m, IH), 7.49 (m, IH), 7.22 (m, 2H), 6.75 (m, 2H), 6.72 (s, IH), 5.43 (s, 2H), 4.66 (s, 2H), 2.07 (s, 3H) . ESHP 4S m/z 498.0143 and 500.0186 (M+H calculated for CnHI 6 BrF 3 NO 5 requires 498.0158 and 500.0141) Step 5: Preparation of 2-[2-({ [3-bromo-l-(2,6difluorophenyl)-6-methyl-2-oxo-l,2-dihydropyridin-4yl]oxy}methyl)-5-fluorophenoxy]-N-ethylacetamide. To a cooled (-10°C) solution of [2- ({ [3-bromo-l- (2 6difluorophenyl) - 6-methyl-2-oxoI, 2-dihydropyridin-4yl]oxy}methyl)-5-fluorophenoxy]acetic acid (from Step 4 (0.15 g, 0.30 mmol) in DMA (2.0 mL) was added 4-methylmorphollne (0.04 mL, 0.36 mmol) and isobutyl chloroformate (0.05 mL, 0.36 mmol). Ethylamine (0.04 mL, 0.45 mmol) was added after minutes. DMF removed by distillation after lh. Crude product purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHCO 3 (30 mL) and extracted in DCM (3 x 25 mL). The organic extracts were dried over Na 2 SO 4 , filtered, concentrated, and dried in vacuo to give a white solid (0.080 g, 51%). IH NMR (CD 3 OD/ 400MHz) 67.60 (m, IH), 7.53 (t, IH, J = 8.0 Hz), 7.23 (t, 2H, J = 8.4 Hz), 6.82 (m, 2H), 6.71 (s, IH), 5.42 (s, 2H), 4.61 (s, 2H), 3.31 (q, 2H, J = 6.4 Hz), 2.10 (s, 3H), 1.09 (t, 3H, J = 7.2 Hz) . ESHRMS m/z 525.0616 and 527.0568 (M+H calculated for C 23 H 21 BrF 3 N 2 0 4 requires 525.0631 and 527.0614). Example 653 methyl 3- [6- [ (acetyloxy)methyl] -3-bromo-4- [(2,4difluorobenzyl)oxy]-2-oxopyridin-!(2H)-yl]-4-methylbenzoate. Step i: Preparation of 3-(2,2-dimethyl-4-oxo-4H-l,3-dioxin-6yl)-2-oxopropyl acetate. 00% b<°O<P m 0 A solution of 2,2,6-trimethyl-4H-l,3-dioxin-4-one (20g, 141 mmol) in dry THF (400 mL) was cooled to -78 °C. To this solution was slowly added a LiHMDS (IM-THF, 160 mL, 160 mmol) . The resulting solution was maintained at -78°C with stirring for 30 min. To the reaction mixture was added acetoxy acetylchloride (17 mL, 160 mmol) and the resulting mixture was maintained at -78 °C for at lh. The reaction was then allowed to slowly warm to rt and stir for an additional lh. The reaction was then quenched with addition of a IN solution of ammonium chloride. The layers were sperated and the aqueous layer was extracted with ethyl acetate (5x). The organics were combined, dried, and concentrated in vacuo. The crude product was purified using a medium pressure liquid chromatography biotage system. Elution with hexanes-ethy] acetate (3:1) gave 13.1 g (38%) of a red-brown oil. The product looks clean by NMR. H NMR (300 MHZ, CDCI 3 ) 6 5.42 (s, IH) , 4.75 (s, 2H) , 3.41 (s, 2H), 2.22 (s, 3H}, 1.75 (s, 6H) . Step 2: Preparation of methyl 3-[6-[(acetylox>')methyl]-4hydroxy-2-oxopyridin-i (2H) -y!] -4-methylbenzoate. OH O To a I00 mL RBF containing methyl 3-amino,4- methylbenzoate (1.65g, i0 mmol) was added the enone from Step 1 (2.6g, 10.7 mmol). The mixture was then dissolved in toluene (40 mL), fitted with a reflux condenser, and placed in an oil bath preset to 115 °C. The mixture was heated to reflux for 1.5h. The reaction flask was removed from the oil bath and a catalytic amount of TFA (5-6 drops) was added. The reaction was placed back in the oil bath and heated to reflux for an additional 2h. The reaction was then allowed to cool to 0°C. The toluene was then removed under vacuum to give a thick brown residue. The residue was then dissolved in acetonitrile (10-15 mL) and allowed to stand. After 20-30 min a precipitate results which was filtered and washed with diethyl ether. After drying, an off-white solid (l.9g, 57% yield) was obtained. IH NMR (300 MHz, DMSO 6 ) 6 7.94 (dd, J = 7.8,1.5 Hz, IH) , 7.73 (s, IH), 7.54 (d, J = 8.1 Hz, IH), 6.19 (s, IH) , 5.73-5.71 (m, IH) , 4.47 (AB quar, J = 10.5 Hz, 2H) , 3.87 (s, 3H), 2.09 (s, 3H), 1.91 (s, 3H) . ES-HRMS m/z 332.1096 (M+H calcd for CIvHIsNO 6 requires 332.1129). Step3: Preparation of methyl 3-[6-[.(acetyloxy)methyl]-3br 0 m 0_ 4_hydr 0 xy-20 x 0 pyridin-l(2H)-yi]-4-methylbenzoate. To a slurry of the phenol (2.5g, 7.5 mmol) in dry acetonitrile (50 mL), at rt, was added n-bromosuccinimide (1.33g, 7.5 mmol) . The resulting homogeneous mixture was stirred at rt for 3h. The resulting precipitate was filtered and washed sequentially with acetonitrile and the diethy! ether. The product was dried in a vacuum oven to yield an off-white solid (2.5g, 81%). IH NMR (300 MHz, DMSO_d 6 ) 6 11.82 (s, IH) , 7.97 (dd, J = 7.8,1.5 Hz, IH), 7.80 (d, J = 1.5 Hz, IH), 7.57 (d, J = 8.1 Hz, IH), 6.38 (s, IH), 4.49 (AB quar, J = 13.8 Hz, 2H), 3.87 (s, 3H), 2.08 (s, 3H), 1.92 (s, 3H) . ESHRMS m/z 410.0225 (M+H calcd for CIvHITNBrO 6 requires 410.0234). Step 4: Preparation of the title compound. To a solution of the above phenol (2.5g, 6.0 mmol) in dry DMF (25 mL) was added solid potassium carbonate (804 mg, 6.0 mmol) . To this mixture was then added, via syringe, 2,4-diflourobenzyl bromide (783 ML, 6.0 mmol) . The resulting mixture was allowed to stir at rt overnight. The reaction was then poured into ice water and stirred vigorously. The resulting precipitate was filtered and washed sequentially with water and diethyl ether. The solid was dried in a vacuum oven to yield an off-white solid 1.90 (s, 3H) . ES-HRMS m/z 536.0484 (M+H calcd for C 24 H INF BrO requires 536.0515) . Example 654 OH 0== 0 Br OH F 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)- 2-oxopyridin-l(2H)-yl]-4-methylbenzoic acid. To a stirred suspension, at rt, of the Example 643 (2.0g, 3.7 mmol) in THF (i0 mL) was added a solution of 2.5N NaOH (3mL, 7.5 mmol). The resulting homogeneous solution was stirred for 2h. The reaction was judged complete and IN HCI was added dropwise until a pH - 4 was obtained. The reaction was then diluted with CH=CI= (i0 mL). The resulting precipitate was filtered with additional washing from CH 2 C1 2 . The solid was dried in a vacuum oven to yield a pure white solid (l.8g, 99%). IH b-MR (300 MHz, DMSO.d 6 ) 5 7.95 (dd, J = 7.8,1.8 Hz, IH), 7.74-7.66 (m, 2H), 7.54 (d, J = 8.1 Hz, IH), 7.37 (dq, J = 7.8, 2.7 Hz, IH), 7.24-7.17 (m, IH), 6.72 (s, IH), 5.39 (s, 2H), 3.83 (AB quar, J = 15.6 Hz, 2H), 2.02 (s, 3H). ES-HRMS m/z 480.0253 (M+H calcd for C 21 HITNF 2 BrOs requires Example 655 HO NH OH F 3_[ 3-br 0 m 0-4-[(2,4-diflu 0 r 0 benzyl)oxy]-6-(hydroxymethyl)- 2-oxopyridinI (2H) -yl ] -N- (2-hydroxyethyl) - 4 -me hylbenzamide. To a slurry of Example 654 (500mg, 1.04 mmol) in anhydrous CH 2 CIc was added EtaN (218 NL, 1.56 mmol) and the resulting homogeneous mixture was stirred at ft. To this mixture was then added ethanolamine (70 ML, 1.14 mmol) via syringe. HOBt (155mg, 1.14 mmol) was then added fol!owed by addition of EDC (217 mg, 1.14 mmol) . The reaction was allowed to stir overnight at ft. The reaction was quenched by addition of a solution of IN NH 4 CI. The biphasic mixture was separated and the aqueous layer was extracted with CH 2 C1 2 (4X). The organics were combined, dried, and concentrated in vacuo. The resulting residue was purified by flash chromatography on a 16g Michele-Miller column. Elution with CH 2 CI 2 -MeOH (I0:i- 12:1) resulted in obtaining the desired product as a viscous oil. The oil was then dissolved in a CH CN-Et 2 0 combination. After 5-10 minutes, a precipitate resulted which upon filtration and drying yielded a pure white solid (210 mg, 2H), 3.39-3.25 (m, 2H), 2.00 (s, 3H). ES-HRMS m/z 523.0674 (M+H calcd for C 23 HnN 2 F 2 BrOs requires 523.0675). Example 656 NH OH F 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)- 2-oxopyridin-l(2H)-yl]-N,4-dimethylbenzamide. The titled compound was prepared from the acid Example 654 (550 mg, 1.07 mmol) in a similar manner to the amide described above using EDC (245 mg, 1.28 mmol), HOBt (171 L, 1.28 mmol), Et 3 N (225 mL, 1.6 mmol), and 2.0M MeArH 2 -THF (1.2 L, 2.48 mmol) . Following work-up with IN NH 4 CI the product was precipitated out of the biphasic mixture after dilution with additional CH 2 C1 2 to give a white solid (250 mg, 51% yield). %). IH NMR (300 MHz, DMSO.d 6 ) 6 8.48 (quar, J = 4.5 Hz, IH), 7.88 (dd, J = 8.1, 1.8 Hz, IH), 7.72 (app quar, J = 6.6 Hz, IH), 7.63 (d, J = 1.8 Hz, IH), 7.52 (d, J = 8.1 Hz, IH), 7.37 (dr, J = 10.2, 2.4 Hz, IH), 7.20 (app dt, J = 8.4, 1.8 Hz, IH) , 6.74 (s, IH) , 5.71 (t, J = 5.4 Hz, IH) , 5.42 (s, 2H), 4.03 (dd, J = 13.8, 5.1 Hz, IH), 3.72 (dd, J = 16.4, 5.1 Hz, IH), 2.78 (d, J = 4.5 Hz, 3H), 2.02 (s, 3H) . ES-HRMS m/z 493.0575 (M+H calcd for C 22 H 20 N 2 F 2 BrO 4 requires 493.0569). Example 657 NH 2 OH F 3- [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-2oxopyridin-l(2H)-yl]-4-methylbenzamide. To a stirred suspension, at rt, of the carboxylic acid Example 654 (400 mg, 0.80 mmol) in anhydrous THF (4 mL) was added 4-methylmorpholine (274 #L, 2.5 mmol). To the resulting heterogeneous solution was then added 2-Chloro-4,6dimethyltriazine (170 mg, 1.0 mmol) and the mixture was allowed to stir for lh at rt. Ammonium hydroxide solution (28-32%, 2 mL) was then added to the reaction and it was allowed to stir at rt overnight. The reaction was then worked up by diluting with H 2 0 (2-3 mL) and stirring vigorously. The resulting precipitate was filtered and washed with H20 and then diethyl ether. After drying with a vacuum oven an off- white solid (140 mg, 32%) was obtained. %). IH NMR (300 MHz, DMSO-d ) 6 7.99-7.80 (m, 2H), 7.76 (m, 3H), 7.52 (d, J = 8.1 Hz, IH), 7.43-7.39 (m, 2H), 7.52 (d, J = 8.1 Hz, IH), 7.43-7.36 (m, 2H), 7.20 (dt, J = 8.7, 1.8 Hz, IH), 6.74 (s, IH) , 5.41 (s, 2H), 4.02-3.62 (m, 2H) 0 2.03 (s, 3H) . ES-HRMS m/z 479.0411 (M+H calcd for C 21 HzBN 2 F 2 BrO 4 requires 479.0413) . Example 658 [(methylamino)carbonyl]phenyl}-6-oxo-l,6-dihydropyridin-2yl)methyl acetate. To a solution of 3- [3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-(hydroxymethyl)-2-oxopyridin-l(2H)-yl]-N,4dimethylbenzamide, (225 mg, 0.50 mmol) stirred in CH 2 C1 2 was added pyridine (55 ML, 0.69 mmol). To the resulting homogeneous solution was then added acetic anhydride (47 NL, 0.51 mmol). The mixture was stirred at rt for 3h. Additiona! pyridine (150 ML, 1.8 mmol) and acetic anhydride (i00 ML, 1.05 mmol) were then added and the reaction was allowed to stir overnight at rt. The reaction was then quenched with IN NHCI and diluted with CH 2 C1 2 . The layers were separated and the organic layer was then extracted with CH 2 C1 2 (3X) . The organics were then combined, dried, and concentrated in vacuo. The residue was then triturated with Et 2 0 and filtered to give (150 mg, 61%) an off-white solid. IH NMR (300 M14z, DMSO_d ) 6 8.48 (br s, IH), 7.87 (app d, J = 7.8 Hz, iH), 7.74-7.69 (m, 2H), 7.52 (d, J = 7.5 Hz, IH), 7.40 (app t, J = 8.1 Hz, IH), 7.28-7.19 (m, IH), 6.91 (s, IH), 5.43 (s, 2H), 4.60 (s, 2H), 2.79 (s, 3H), 2.06 (s, 3H), 1.94 (s, 3H) . ES-HRMS m/z 535.0676 (M+H calcd for C 24 HnN 2 F 2 BrOs recg/ires 535.0675). Example 659 oxopyridin-l(2H}-yl]-N-methylbut-2-enamide. Step I, (2E)-4-[3-bromo-4-[(2,4~difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]but-2-enoic acid: The carboxylic acid compo was prepared by stirring the ester (900 mg, 2.1 mmol) in THF (i0 mL). To this solution was added IN NaOH (i mL) and the resulting mixture was stirred at ft. After 2 h, additional NaOH (I mL) was added to the reaction and then allowed to stir at rt overnight. The THF was then concentrated under vacuum. The remaining aqueous layer was then acidified to pH - 4 after which a white precipitate resulted. Filtration and drying under vacuum gave rise to a white solid (900 mg) that was used as in the next step. The titled compound was prepared by stirring the above acid (480 mg, 1.16 mmol) in CHIC1 2 at rt. To this mixture was added sequentiallyEt 3 N (244 pL), HOBt (188 mg, 1.4 mmol), MeNH 2 (2.0M-THF, 700 mL, 1.4 mmol), and finally EDC (266 mg, 1.4 mmol). The homogeneous mixture was then allowed to stir at rt overnight. The reaction was quenched with IN HCI. The layers were separated and the aqueous layer was extracted with CH 2 C1 2 (4x). The organics were combined, dried, and concentrated in vacuo. The crude residue was triturated in CH CN-Et 2 0 combination and filtered to give a pure white solid (330 mg, IH), 2.61 (d, J = 4.S Hz, 3H), 2.37 (s, 3H). ES-HRMS m/z 427.0493 (M + H calcd for C 1 eH 1 sBrF N 2 0 3 = 427.0463) . Example 660 O OCH 3 methyl 5-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyi-2oxopyridin-l(2H)-yl]methyl}-2-furoate Step I: To a room temperature suspension of 3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one (330.1 mg, 1.00 mmol)) and NaH (48.0 mg, 2.0 mmol) in THF (1.6 mL) was added methyl-5-chloromethyl-2-furate (400 mg, 2.30 mmol) . The resulting suspension was stirred and heated to 68 °C for 8 hours until complete consumption of starting material by LCMS analysis. The reaction mixture was then diluted with ammonium chloride (saturated aqueous solution, i0 mL) and water (i00 mL). This resulting emulsion was then extracted with with ethyl acetate (3 X 300 mL). The resulting organic extract was separated, Na 2 S0 4 dried, and concentrated. The resulting dark residue was subjected to SiO 2 chromatography with ethyl acetate/hexanes (3:7) to furnish a solid. IH NMR (400 MHz, CDCI 3 ) 6 7.53 (app q, J = 8.2 Hz, IH), 7.07 (d, J = 3.5 Hz, IH), 6.93 (app dt, J = 8.4, 1.5 Hz, IH), 6.84 (app ddd, J = 10.2, 8.7, 2.4 Hz, IH) , 6.53 (d, J = 3.4 Hz, IH) , 6.00 (s, IH) , 5.27 (s, 2H) , 5.18 (s, 2H) , 3.85 (s, 3H) , 2.54 (s, 3H) ; LC/MS C-18 column, tr = 2 • 64 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 468 (M+H) . ES-HRMS m/z 468.0276 (M+H calcd for C 20 HI BrF 2 NOs requires 468.0253). Example 661 NH O= O Br 3- [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-4-(hydroxymethyl)-N-methylbenzamide Step I: Preparation of 2-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4- [(methylamino) carbonyl] benzoic acid F OH H TO a room temperature solution of methyl 2-[3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4- [(methylamino)carbonyl]benzoate (1.05 g, 2.02 mmol) in THF (10.0 mL) was added dropwise an aqueous solution of sodium hydroxide (3.0 M, 3.5 mL, I0 mmol) . The reaction was then heated to 60 °C for 8.0 hours. The resulting suspension was then diluted with 500 mL of ethyl acetate and neutralized with an aqueous solution of hydrochloric acid (2.0 N, 5.0 mL, I0 mmol). The resulting biphasic solution was separated and the resulting aqueous layer was further extracted with ethyl acetate (2 X 200 mL) . The resulting combined organic extracts were Na 2 SO 4 dried, filtered and concentrated in vacuo to a volume of 50 mL. At this time a white solid began to form and the resulting solid suspension was allowed to sit until precipitation appeared to stop (approximately 1.0 hour). The precipitate was collected and dried in vacuo (i.0 mm Hg) to furnish the solid acid as an intermediate (806 mg, 78 %). IH NMR (400 MHz, d ~DMF) 6 13.19 (s, IH), 8.63 (app d, J = 4.5 Hz, IH), 8.09 (d, J = 8.0 Hz, IH), 8.00 (dd, J = 8.0, 1.6 Hz, IH) , 7.71-7.67 (m, 2H), 7.34 (app dt, J = 9.6, 1.6 Hz, IH), 7.16 (app dt, J = 8.7, 1.8 Hz, IH), 6.66 (s, IH), 5.33 (s, 2H), 3.29 (s, 3H), 1.92 (s, 3H); LC/MS C-18 column, tr = 2.15 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 507 (M+H) . ES-HRMS m/z 507.0344 (M+H calcd for C 2 HI 6 BrF 2 N 2 0 5 requires 507.0362). Step 2: Preparation of the title compound . To a 0 °C solution of 2-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]-4-[(methylamino)carbonyl] benzoic acid (500 mg, 0.986 mmol) in THF (6.8 mL) was added dropwise a solution of borane-dimethyl sulfide complex (THF solution, 2.0 M, 2.0 mL, 4.0 mmol). The internal temperature of the reaction was never allowed to exceed 0 °C. The resulting solution was maintained for 4.0 hours, at which time the cooling bath was removed and the reaction was maintained at room temperature for an additional two hours. Next, a solution of ammonium chloride (saturated aqueous, 300 mL) was added. The resulting emulsion was extracted with ethy! acetate (3 X 300 mL) and the resulting organic extracts were separated, Na 2 SO 4 dried, and concentrated in vacu0 to a residue that was subjected to SiO 2 chromatography with ethyl acetate/hexanes (6:4) to furnish a solid (392 mg, 81%). IH NMR (400 MHz, d 4 ~ MeOH) 5 7.96 (dd, J = 8.0, 1.9 Hz, IH), 7.75 (d, J = 8.1 Hz, IH), 7.65 (app q, J = 8.0 Hz, IH), 7.58 (d, J = 1.7 Hz, IH), 7.05 (app t, J = 8.5 Hz, 2H), 6.64 (s, IH), 5.36 (s, 2H), 4.35 (AB-q, J = 14.1 Hz, A= 60.8 Hz, 2H), 2.90 (s, 3H), 2.03 (s, 3H) ; LC/MS C-18 column, tr = 2.16 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 493 (M+H) . ES-HRMS m/z 493.0590 (M+H calcd for C 22 H 0 BrF 2 N 2 0 requires 493.0596). Example 662 HN Br" 2- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl2-oxopyridin1 (2H) -yl] -N, N' -dimethylterephthalamide Step i: To a room temperature solution of 2-[3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4- [(methylamino)carbonyl] benzoic acid (500 mg, 0.986 mmol) in DMF (5.0 mL) was added l-(3-dimethylaminopropyl)- ethylcarbodiimide hydrochloride (EDC-HCI, 350.0 mg, 1.83 mmol) and l-hydroxy-benzotriazole (HOBT, i00.0 mg, 0.74 mmol) sequentially. To this resulting suspension was then added a solution of methylamine (2.0 M THF, 1.0 mL, 2.0 mmol). The reaction was stirred for 16.0 hours, at which time the reaction was diluted with ethyl acetate (600 mL) . The mixture was washed with (3 X 200 mL) of water and the organic extract was separated, Na 2 S0 4 dried, and concentrated in vacuo to a volume of approximately 60 niL. At this time a solid precipitate formed and was collected to furnish (289 mg, 56 %). IH NMR (300 MHz, d 4 -MeOH) 6 8.06 (br d, J = 8.0 Hz, IH), 7.81 (d, J = 8.1 Hz, IH), 7.73 (s, IH), 7.70 (app q, J = 7.4 Hz, IH) , 7.09 (app t, J = 8.0 Hz, 2H) , 6.65 (s, IH) , 5.39 (s, 2H), 2.96 (s, 3H), 2.79 (s, 3H), 2.13 (s, 3H) ; LC/MS C-18 column, tr = 2.13 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min with detection 254 rim, at 50°C) . ES-MS m/z 520 (M+H) . ES-HRMS m/z 520.0700 (M+H calcd for C 23 H 21 BrF 2 N]O 4 requires 520.0678). Example 663 !(2H)-yl]-N-4-methylterephthalamide Step i: To a room temperature suspension of 2-[3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-y!]-4- [(methylamino)carbonyl] benzoic acid (302 mg, 0.595 mmol) in THF (1.8 mL) was added 2-chloro-4,6 dimethoxy-l,3,5 triazine (140.5 mg, 0.800 mmol) and N-methyl morpholine (NMM, 184 mg, 1.824 mmol) sequentially. The resulting solution was matured for 2 hours and then a saturated aqueous solution of ammonium hydroxide (0.60 mL) was added. The reaction was allowed to continue for 1 additional hour at which time a precipitate formed which was collected, washed with 20 mL of diethyl ether, and dried in vacuo to furnish a solid (201 mg, 66 %). iH NMR (400 MHz, d 6 -DMSO) 6 8.59 (br d, J = 8.0, IH), 7.96 (d, J = 8.0 Hz, IH), 7.83 (s, IH), 7.72 (d, J = 9.0, IH), 7.697.64 (m, 2H) , 7.39-7.31 (m, IH) , 7.19 (app t, J = 8.0 Hz, IH) 6.60 (s, IH), 5.31(s, 2H), 3.85 (s, IH), 2.78 (br d, J = 8.0 Hz, 3H) , 1.96 (s, 3H) ; LC/MS C-18 column, tr = 2.20minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 506 (M+H). ES-HRMS m/z 506.0550 (M+H calcd for C 22 HIgBrF 2 N 3 0 4 requires 506.0522). Example 664 methyl 4- (aminocarbonyl) -2- [3-bromo-4-[(2,4di f luorobenzyl ) oxy] - 6 -methyl - 2 - oxopyridin1 (2H) -y! ] benzoate Step i: To a room temperature solution of 3-(4-hydroxy-6methyl-2-oxopyridin-l(2H)-yl)-4-(methoxycarbonyl)benzoic acid (3.01 g, 9.93 mmol) in DMF (20 mL) was added 1-(3dimethylaminopropyl)-ethylcarbodiimide hydrochloride (EDC-HCI, 2.00 g, 10.4 mmol) and l-hydroxy-benzotriazole (HOBT, 50.0 mg, 0.367 mmol) sequentially. To this resulting suspension was then added a solution of ammonia (0.5 M 1,4 dioxane, 30.0 mL, 15.0 mmol). The reaction was stirred for 16.0 hours until complete consumption of starting material was seen by LCMS analysis. At this time the reaction vessel was placed on a roto-evaporator at 30 mm Hg vacuum and maintained at 30 °C for minutes to strip off any residual ammonia from the reaction mixture. The reaction vessel was removed from the rotoevaporator and subsequently charged with solid Nbromosuccinimide (1.790 g, 10.06 mmol) and the resulting reddish solution was stirred for 3.0 hours. At this time the reaction was charged with K 2 CO (3.00 g, 21.7 mmol) and 2,4 difluorobenzyl bromide (1.95 mL, 15.2 mmol). The resulting suspension was stirred for 16.0 hours. At this time the reaction suspension was diluted with water (400 mL) and extracted with ethyl acetate (3 X 300 mL). The organic extracts were separated, Na 2 SO 4 dried, and concentrated to a residue that was subjected to SiO 2 chromatography using ethyl acetate/hexanes/methanol (6:3.5:0.5) to furnish an off white solid (1.09 g, 21%). IH NMR (400 MHz, d 4 -MeOH) 6 8.21 (dd, J : 8.5, 1.5 Hz, IH), 8.09 (dd, J = 7.6, 2.0 Hz, iH), 7.78 (hr s, IH), 7.65 (app q, J = 7.9 Hz, IH), 7.03 (app t, J = 8.0 Hz, 2H), 6.63 (s, IH) , 5.37 (s, 2H), 3.75 (s, 3H), 2.02 (s, 3H) ; LC/MS C-18 column, tr = 2.28 minutes (5 to 95% acetonitrile/water over 5 minutes at i ml/min with detection 254 nm, at 50°C) . ES-MS m/z 507 (M+H). ES~HRMS m/z 507.0385 (M+H calcd for C 22 HIeBrF 2 N 2 Os requires 507.0362). Example 665 F N O, O 2- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2 -oxopyridin1 (2H) -yl] -N I ,N I, N 4trimethylterephthalamide Step I: To a room temperature solution of 2-[3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4- [(methylamlno)carbonyl] benzoic acid (300 mg, 0.591 mmol) in DMF (i.8 mL) was added l-(3-dimethylaminopropyl)- ethylcarbodiimide hydrochloride (EDC-HCI, 190.0 mg, 1.0 mmol) and l-hydroxy-benzotriazole (HOBT, 26.0 mg, 0.191 mmol) sequentially. To this resulting suspension was then added a solution of dimethylamine (2.0 M THF, 0.50 mL, 1.0 mmol). The reaction was stirred for 16.0 hours, at which time the reaction mixture was directly applied to SiO 2 chromatography with ethyl acetate/hexanes (6:4) to furnish a solid (206 mg, %). IH N-MR (400 MHz, d 4 -MeOH) 6 8.01 (dd, J = 8.2, 1.5 Hz, IH), 7.73 (app d, J = 8.1 Hz, IH), 7.61 (app q, J = 7.2 Hz, IH), 7.60 (app d, J = 9.5 Hz, IH), 7.04 (app t, J = 8.0 Hz, 2H), 6.65 (s, IH), 5.32 (s, 2H), 3.64 (s, 3H), 2.92 (s, 6H) , 2.13 (s, 3H) ; LC/MS C-18 column, tr = 2.20 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 534 (M+H). ES-HRMS m/z 534.0820 (M+H ca!cd for C 24 H 2 BrF 2 N 3 0 4 requires 534.0835). Example 666 c Br 2-[3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinI(2H)-yI]-4- [(methylamino)carbonyl]benzyl carbamate Step I: To a room temperature solution of 3- [3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4- (hydroxymethyl)-N-methylbenzamide (493 mg, 1.00 mmol) in methylene ch!oride (5.0 mL) was added a solution of trichloroacetyl isocyanate (toluene, 0.53 M, 1.9 mL, 1.0 mmol). The resulting solution was stirred for one hour until complete consumption of starting material by LCMS analysis. The reaction mixture was then directly applied to AI 2 0 (0.5 g of activity type I) and the slurry was matured for three hours. At this time, the AI 2 0 plug was flushed with ethy! acetate/methanol (95:5) and the resulting mother liquor was concentrated to a residue that was subjected to SiO 2 chromatography using ethyl acetate/hexanes/methanol (6:3.5:0.5) to furnish a white solid (396 mg, 74 %). IH NMR 2.10 (s, 3H) ; LC/MS C-18 column, tr = 2.15 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 536 (M+H) . ES-HRMS m/z 536.0617 (M+H calcd for C 23 H IBrF N 3 0 5 requires 536.0627). Example 667 F 3-bromo-4- [ (2,4-difluorobenzyl)oxy]-l- (2,6-difluoro-4vinylphenyl) - 6-methy!pyridin-2 (IH) -one Step i: Preparation of 4-[(2,4-difluorobenzyl)oxy]-l-(2,6difluoro-4-vinylphenyl)-6-methy!pyridin-2(iH)- one O F To a room temperature solution of l-(4-bromo-2,6- difluorophenyl)-4- [(2,4-difluorobenzyl)oxy]-6-methylpyridin2(IH)- one (4.01 g, 9.06 mmol) in anhydrous THF (30mL) was added, sequentially, tributyl(vinyl)tin (5.00 g, 15.7 mmol) and tetrakis(tripheylphosphine)palladium (i.00 g, 0.865 mmol) under an argon stream. The reaction vessel was then equipped with a reflux condenser and the reaction system purged with an argon flow. The resulting yellow solution was heated to 68 °C and stirred under a positive pressure of argon for 12.0 hours until complete disappearance of starting material by LCMS analysis. The reaction mixture was diluted with 300 mL of brine and extracted with ethyl acetate (3 X 300 mL). The organic extracts were separated, Na S0 4 dried, and concentrated in vacuo and the resulting dark residue was subjected to SiO chromatography with ethyl acetate/hexanes (!:!) to furnish a yellowish solid (3.18 g, 90 %). iH NMR (400 MHz, CDCI 3 ) 6 7.41 (app q, J = 8.0 Hz, IH), 7.08 (app d, J = 8.3 Hz, 2H), 6.90 (app t, J =7.2 Hz, IH), 6.85 (app t, J = 7.4 Hz, IH), 6.63 (dd, J = 17.5, 10.9 Hz, IH), 5.96 (app d, 15.8 Hz, IH), 5.94 (app d, J = 15.8 Hz, IH) , 5.79 (d, J = 17.4 Hz, IH) , 5.43 (d, J = 10.9 Hz, IH) , 5.01 (br s, 2H), 1.99 (s, 3H); LC/MS C- 18 column, tr = 2.93 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 390 (M+H). ES-HRMS m/z 390.1095 (M+H calcd for CnH 6 F 4 N0 2 requires 390.1112). Step 2: To a briskly stirred room temperature solution of 4- [(2,4-difluorobenzyl)oxy]-l-(2,6-difluoro-4-vinylphenyl)-6methylpyridin-2(iH)- one (721 mg, 1.85 mmol) in methylene chloride (i0 mL) was added solid N-bromosuccinimide (330 mg, 1.86 mmol) and the resulting reddish solution was stirred for i0 minutes. At this time the reaction was diluted with ethyl acetate (i00 mL) and washed with sodium sulfite (5 % aqueous solution, 50 mL) The resulting organic extracts were Na 2 S0 4 dried, filtered, and concentrated in vacuo to approximately mL volume. The resulting mother liquor rapidly precipitated and furnished an amorphous solid that was collected and dried at 1 mm Hg vacuum to provide a solid (610 mg, 70 %). IH NMR s, 2H) , 2.07 (s, 3H) ; LC/MS C-18 column, tr = 3.17 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 468 (M+H) . ES-HRMS m/z 468.0249 (M+H calcd for C 21 HIsBrF 4 NO 2 requires 468.0217). Example 668 F OH 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-[4-(l,2-dihydroxyethyl)- 2,6-difluorophenyl]-6-methylpyridin-2(iH)-one Step i: Preparation of the title compound To a room temperature solution of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l- (2,6-difluoro-4-vinylphenyl)-6-methylpyridin-2(iH)-one (408.0 mg, 0.871 mmol) in water/acetone 1:3 (8.0 mL) was added, sequentially, N-methyl morpholine oxide (268.0 mg, 2.29 mmol) and osmium tetroxide (4 % water solution, 0.25 mL or approximately i0 mg, 0.039 mmol). The resulting solution was stirred for 8 hours until complete consumption of starting material by LCMS analysis, and the reaction was concentrated in vacuo to onefourth original volume. The resulting solution was diluted with ethyl acetate (300 mL) and washed with water (2 X I00 mL) . The organic extract was separated, Na 2 SO 4 dried, and concentrated in vacuo and the resulting dark residue was subjected to SiO 2 chromatography with ethyl acetate/hexanes/ methanol (6:3.5:0.5) to furnish a solid (389 rag, 88 %). IH NMR (400 MHz, d 4 -MeOH) 6 7.62 (app q, J = 8.0 Hz, IH), 7.26 (dd, J = 9.6, 4.5 Hz, 2H), 7.04 {app t, J = 8.6 Hz, 2H), 6.67 (s, IH) , 5.36 (s, 2H) , 4.75 (app t, J = 5.6 Hz, 1H), 3.68-3.61 (m, 2H) , 2.11 (s, 3H) ; LC/MS C-18 column, tr = 2.26 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 502 (M+H) . ES-HRMS m/z 502.0247 (M+H calcd for C 21 HIvBrF 4 NO 4 requires 502.0272). Example 669 O F 4-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-3,5-difluorobenzaldehyde Step i: Preparation of the title compound To a room temperature solution of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l- [4-(l,2-dihydroxyethyl)-2,6-difluorophenyl]- 6-methylpyridin2(iH)-one (310 mg, 0.615 mmol) in toluene (3.0 mL) was added lead(IV) acetate (443 mg, 1.63 mmol). The resulting dark brown solution was stirred for one hour until complete consumption of starting material by LCMS analysis. The reaction mixture was then diluted with ethyl acetate (i00 mL), water washed (3 X I00 mL), and brine washed (3 X 30 mL) . The resulting organic extract was separated, Na 2 SO 4 dried, and concentrated. The resulting dark residue was subjected to SiO 2 chromatography with ethyl acetate/ hexanes (i:I) to furnish a light yellow solid (269 mg, 93 %). Caution, product is easily air oxidized. H NMR (300 MHz, d 4 -MeOH) 6 10.05 (s, IH), 7.68 (app C-18 column, tr = 2.72 minutes (5 to 95% aceLonisriie/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) ES-MS m/z 470 (M+H) . ES-HRMS m/z 470.0049 (M+H calcd for C= 0 HI 3 BrF 4 NO 3 requires 470.0009). Example 670 F... F 4_[ 3-br 0 m 0-4-[(2,4-diflu 0 r 0 benzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-3,5-difluorobenzyl carbamate Step i: To a room temperature solution of 4-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-3,5- difluorobenzaldehyde (220 mg, 0.468 mmol) in methanol (i0 mL) was added solid sodium borohydride (60.0 mg, 1.58 mmol). The resulting solution evolved gas for approximately 0.5 minute and was stirred for i0 additional minutes until complete consumption of starting material by LCMS analysis. The reaction was then diluted with saturated aqueous solution of ammonium chloride (i0 mL) and extracted with ethyl acetate (4 X 50 mL). The organic extract was separated, Na 2 SO 4 dried, and concentrated to a residue. This resulting residue was then diluted with methylene chloride (5.0 mL) and a solution of trichloroacetyl isocyanate (toluene, 0.53 M, 1.0 mL, 0.53 mmol) was added. The resulting solution was stirred for one hour until complete consumption of starting material by LCMS analysis. The reaction mixture was then directly applied co AI=O 3 (0.5 g of activity type I) and the slurry was matured for three hours. At this time, the A1 2 0 3 plug was flushed with ethyl acetate/methanol (95:5) and the resulting mother liquor was concentrated to a residue that was subjected to SiO 2 chromatography using ethyl acetate/hexanes/methanol (6:3.8:0.2) to furnish a white solid (181 mg, 75 %). IH NMR (400 MHz, d 4 -MeOH) 6 7.63 (app q, J -- 8.0 Hz, IH) , 7.43 (d, J 8.2 Hz, 2H), 7.04 (app t, J = 8.1 Hz, 2H) , 6.68 (s, IH), 5.37 (s, 2H) , 5.12 (m, 2H) , 2.11 (s, 3}{) ; LC/MS C-18 column, tr = 2.54 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 515 (M+H). ES-HRMS m/z 515.0232 (M+H calcd for C IHI 6 BrF 4 N 2 0 4 requires 515.0234) . Example 671-687 The following compounds are prepared essentially according to the procedures outlined in the schemes and the above examples Example No, Example No. Exampl F 672 F e 671 Example 701 O H N-(4-{[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}benzyl)-2-hydroxyacetamide Step i. Preparation of l-[4-(aminomethyl)benzyl]-3-chloro-4- [(2,4-difluorobenzyl}oxy]-6-methylpyridin-2(iH)-one. The compound of Example 606 (i0.0 g, 23.38 mmol) was suspended in tetrahydrofuran (I00 mL) and cooled in an ice-bath. Borane dimethyl sulfide (29.9 mL, 2.0 M in tetrahydrofuran, 59.7 mmol) was added. The resulting mixture was heated to reflux overnight and then cooled in an ice-bath. Additional borane dimethyl sulfide (5.85 mL, 2.0 M in tetrahydrofuran, 11.7 mmol) was added. The resulting mixtue was heated to reflux overnight and the cooled to room temperature. The flask was fitted with a distillation head and the reaction was partially concentrated. Additional borane dimethyl sulfide (5.85 mL, 2.0 M in tetrahydrofuran, 11.7 mmol) was added. The mixture was heated to reflux overnight and the cooled in an ice-bath. The reaction was quenched by the addition of 1.0 N HCI (75.0 mL) then partially concentrated. The aqueous layer was made alkaline with 2.5 N NaOH and a precipitate developed. The solid was collected by filtration washing with diethyl ether to give a pale purple solid (3.00 g, 32 %). XH NMR (400 MHz, DMSO-d 6) 6 7.64 (app q, J = 7.9 Hz, IH), 7.44 (d, J = 7.9 Hz, 2H), 7.32 (app dt, J = 2.4, 9.9 Hz, IH), 7.14 (app dr, J = 1.9, 8.5 Hz, IH), 7.13 (d, J = 7.9 Hz, 2H), 6.61 Is, IH), 5.27 (s, 4H), 3.90 (s, 2H), 2.29 (s, 3H) . Step 2. Preparation of N- (4-{ [3-chloro-4- [(2,4di f luorobenzyl ) oxy] - 6 -methyl -2 -oxopyridin1 ( 2 H) - yl ] methyl } benzyl ) - 2 -hydroxyacetamide. Acetoxyacetic acid (1.46 g, 12.35 mmol) was dissolved in N,Ndimethylformamide (30 mL) and l-Hydroxybenzotriazole (1.84 g, 13.59 mmol) was added followed by 4-methylmorpholine (2.04 mL, 18.53 mmol), l-[4-(aminomethyl)benzyl]-3-chloro-4- [(2,4difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one (compound of step i) (2.50 g, 6.18 mmol) and then 1-[3- (dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (2.84 g, 14.83 mmol) . The resulting mixture was stirred at room temperature for I hour at which time the reaction was diluted with H 2 0 (i00 mL). The reaction mixture was then extracted with ethyl acetate. The combined organic extracts were washed with saturated NaHC0 3 , brine, dried over Na S0 4 , filtered and concentrated. Chromatography (silica gel, hexanes/ethyl acetate with 10% methanol) provided a white foam. The resulting foam was dissolved in 10% aqueous methanol (20 mL) . K 2 C0 3 (0.653 g, 4.73 retool) was added and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concen -rated and H20 (50 mL) was added. The resulting precipitate was collected by filtration washing with diethyl ether to give an off-white solid (1.34 g, 47%) . IH NMR (400 MHz, CDCI 3 ) 6 7.50 (app q, J = 7.7 Hz, IH), 7.27 (app t, J = 5.8 Hz, IH), 7.12 (d, J = 8.1 Hz, 2H), 6.97 (d, J = 8.1 Hz, 2H), 6.94-6.89 (m, IH), 6.86-6.81 (m, IH), 6.09 (s, 2H) , 5.23 (s, 2H), 5.18 (s, 2H), 4.53 (t, J = 5.8 Hz, IH), 4.33 (d, J = 5.9 Hz, 2H) , 3.85 (d, J = 5.6 Hz, 2H), 2.30 (s, 3H). ES-HRMS m/z 463.1256 (M+H calcd for C 23 H 22 CIF _N 0 2 0 4 requires 463.1231). Example 702 F N-(4-{ [3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]methyl}benzyl)-lhydroxycyclopropanecarboxamide Preparation of N- (4-{ [3-chloro-4- [ (2,4-difluorobenzyl)oxy] -6methy!-2-oxopyridin1 (2H) -yl] methyl }benzyl) - lhydroxycyc 1 opropane carboxamide, l - Hydroxy1 - cyc 1 opropane ~ carboxyiic acid (1.26 g, 12.35 mmol) was dissolved in N,Ndimethylformamide (30 mL) . i-Hydroxybenzotriazole (1.84 g, 13.59 mmol) was added followed by 4-methy]morpholine (2.04 mL, 18.53 retool) , i- [4- (aminomethyl)benzyl]-3-chloro-4- [(2,4difluorobenzyl)oxy]-6-methylpyridin-2(1H) -one (Example 701, step I) (2.50 g, 6.18 retool) and then 1-[3- (dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (2.84 g, !4.83 mmol). The resulting mixture was stirred at room temperature for 24 hours at which time the reaction was diluted with H 2 0 (i00 mL) . The reaction mixture was then extracted with ethyl acetate. The combined organic extracts were washed with saturated NaHCO 3 , brine, dried over Na 2 SO 4 , filtered and concentrated. Chromatography (silica gel, hexanes/ethyl acetate with 10% methanol) provided a white foam. The resulting foam was dissolved in 10% aqueous methanol (20 mL) to provide an white foam (1.45 g, 48%). IH NMR (400 MHz, CDCI 3 ) 6 7.52-7.46 (m, IH), 7.34 (t, J = 5.9 Hz, IH), 7.08 (d, J = 8.2 Hz, 2H), 6.92 (app d, J = 8.2 Hz, 2H), 6.92-6.89 (m, IH), 6.86-6.81 (m, IH), 6.11 (s, IH), 5.22 (s, 2H), 5.18 (s, 2H), 4.30 (d, J = 5.9 Hz, 2H), 2.28 (s, 3H) , i. Ii (app q, J = 4.1 Hz, 2H), 0.90 (app q, J = 4.1 Hz, 2H) . ES-HRMS m/z 489.1420 (M+H calcd for C 25 H 24 CIF 2 N 2 0 4 requires 489.1387). Example 703 4- { [3-bromo-4- [ (2,4-dif!uorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H)-yl]methyl}benzyl carbamace Preparation of 4-{ [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]methyl}benzyl carbamate Compound of Example 206 (0.868 g, 1.93 mmol) was suspended in dichloromethane (7.0 mL) . Trichloroacetyl isocyanate (4.00 mL, 0.53 M in toluene, 2.12 mmol) was added. The resulting mixture was stirred at room temperature for 3 hours then diluted with tetrahydrofuran (50 mL) and A1203 (5.0 g) was added and the mixture was stirred at room temperature overnight. The reaction mixture was filtered through a pad of Celite® washing with methonal. The filtrate was then concentrated and the residue was redissolved in tetrahydrofuran (30 mL). Ai 2 0 3 (5.0 g) was added and the mixture was heated to 40 oC for 3 hours. After cooling to room temperature, the reaction was filtered through a pad of Celite ® washing with methanol. The filtrate was concentrated and the resulting solid was washed with diethyl ether to give an off-white solid (0.831 g, 87%). IH NMR (400 MHz, CDCI ) 7.54 (app q, J = 7.7 Hz, IH), 7.25 (d, J = 8.2 Hz, 2H), 7.13 (d, J = 8.2 Hz, 2H), 6.25 (app dt, J = 2.0, 8.3 Hz, IH), 6.866.30 (m, IH), 5.97 (s, IH), 5.32 (s, 2H) , 5.18 (s, 2H), 5.02 (s, 2H), 4.81 (br s, 2H), 2.25 (s, 3H). ES-HRMS m/z 493.0580 (M+H calcd for C 2 H 0 BrF 2 N=O 4 requires 493.0569). Example 704 F o<H 2- [ (4- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-2oxopyridin1 (2H) -yl ] methyl }phenyl) amino] - l-methyl-2-oxoethyl acetate To a reaction vessel (borosilicate culture tube) was added compound of Example 611 (0.300 g, 0.69 mmol) and dichloromethane (3.0 mL) . A stock solution of Nmethylmorpholine (0.30 M, 3.0 mL) was added and the parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for i0 minutes. (S)-(-)-2-Acetoxypropionyl chloride (0.131 mL, 1.04 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature for 1.5 hours. At this time the reaction was diluted with dichloromethane (20 mL) and treated with approximately 2.1 g of polyamine resin (2.63 mmol/g) and approximately 3.8 g of methylisocyanate fucntionalized polystyrene (I.i0 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature overnight. The reaction vessel was then opened and the solution Phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were rinsed with dichloromethane (2 x I0 mL) . The filtrate was evaporated by blowing N 2 over the vial to afford an off-white solid (0.375 g, 99%). !H NMR (400 MHz, DMF-d 6 ) 6 I0.14 (s, IH) , 7.75 (app dt, J = 6.98, 8.59 Hz, !H), 7.67-7.64 (m, 2H) , 7.30 (ddd, J = 2.55, 9.26, 11.81 Hz, IH), 7.21-7.17 (m, 3H) , 6.61 (s, IH) , 5.37 (s, 4H), 5.11 (q, J = 6.85 Hz, IH), 2.40 (s, 3H) , 2.10 (s, 3H) , 1.46 (d, J = 6.$5 Hz, 3H) . ES-HRMS m/z 549. 0790 (M+H calcd for C 2 sH 23 BrF 2 N 2 Os requires 549. 0831). Example 705 F-.. 2- [ (4- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin1 (2H) -yl ] methyl }phenyl ) amino] - I, 1 -dimethyl - 2 - oxoethyl acetate By the method for Example 704 and substituting (S)- (~)-2acet oxypropionyl chloride with 2-acetoxy2 -methylpropionyl chloride, the title compound was prepared (0.380 g, 98%). IH NMR (400 MHz, DMF-d 6 ) 6 9.68 (s, IH), 7.75 (app dt, J = 6.72, 8.60 Hz, IH) , 7.71-7.68 (m, 2H) , 7.30 (ddd, J = 2.55, 9.40, 11.95 Hz, IH) , 7.21-7.15 (m, 3H) , 6.61 (s, IH) , 5.37 (s, 4H) , 2.41 (s, 3H) , 2.04 (s, 3H) , 1.59 (s, 6H) . ES-HRMS m/z 563.1027 (M+H calcd for C 2 H 2 sBrF 2 N 2 Os requires 563.0988). Example 706 F O H 2 N" {i- [3- (aminocarbony!)phenyl]-5-chloro-4- [(2,4difluorobenzyl) oxy] - 6-oxoi, 6-dihydropyridin2-yl }methyl acetate Step I: Preparation of {1-[3-(aminocarbonyl)phenyl]-4hydroxy-6-oxo-l,6-dihydropyridin-2-yl}methyl acetate. O HQ O 3-(2,2-dimethyl-4-oxo-4H-l,3-dioxin-6-yl)-2-oxopropyl acetate (4.00 g, 16.52 mmol) was dissolved in 1,4-dioxane (160 mL) and 3-aminobenzamide (1.73 g, 12.71 mmol) was added. The reaction was heated to reflux for 1 hour then cooled to 70 °C. Methanesulfonic acid (1.22 g, 12.71 mmol) was added and the reaction brought back to reflux for 1 hour. The reaction was cooled to room temperature, concentrated and used as crude product for the next step. Step 2: Preparation of {l-[3-(aminocarbonyl)phenyl]-4-[(2,4difluorobenzyl)oxy]-6-oxo-l,6-dihydropyridin-2-yl}methyl acetate dihydropyridin-2-yl}methyl acetate (crude from step I) (3.61 g, 11.94 mmol) was dissolved in N,N-dimethylformamide (40 mL) . K 2 CO (3.80 g, 27.46 mmol) was added followed by 2,4dif!uorobenzyl bromide (5.44 g, 26.27 mmol) . The reaction mixture was stirred for 48 hours at room temperature. The reaction mixture was then partially concentrated and the residue taken up in dichloromethane/tetrahydrofuran i:i and filtered. The filtrate was collected, concentrated and the residue tritrated with dichloromethane to afford a tan solid (1.64 g, 32%). IH NMR (400 MHz, DMF-d 6 ) 6 8.19 (br s, IH) , 8.07 (app dr, J = 1.35, 7.66 Hz, IH), 7.91 (app t, J = 1.81 Hz, IH) , 7.76 (app dt, J = 6.58, 8.59 Hz, IH) 7.62 (t, J = 7.79 Hz, IH), 7.55 (ddd, J = 1.21, 2.01, 7.79 Hz, IH), 7.46 (br s, IH), 7.34 (ddd, J = 2.55, 9.40, 10.47 Hz, IH), 7.237.18 (m, IH), 6.26 (d, J = 2.55 Hz, IH), 6.11 (d, J = 2.69 Hz, IH), 5.23 (s, 2H), 4.62 (AB q, J = 14.97 Hz, 2H), 1.96 (s, 3H). ES-HRMS m/z 429.1280 (M+H calcd for C 22 HIsF 2 N 2 0 5 requires 429.1257). Step 3: Preparation of the title compound {l-[3-(aminocarbonyl)phenyl]-4-[(2,4-difluorobenzyl)oxy]-6oxo-l,6-dihydropyridin-2-yl}methyl acetate (from step 2) (1.02 g, 2.39 mmol) was suspended in dichloromethane (15 mL) and Nchlorosuccinimide (0.37 g, 2.75 mmol) was added. Dichloroacetic acid (0.i0 ml, 1.22 mmol) was added and the reaction mixture was stirred at 40 °C for 1.5 hours. The reaction was cooled to room temperature and a precipitate formed. The reaction mixture was diluted with diethyl ether and the precipitate was collected by filtration and washed with diethyl ether (3 x 15 mL) to afford a tan solid (0.940 g, 85%). IH NMR (400 MHz, DMF-d 6 ) 6 8.21 (br s, IH), 8.11 (apR dt, J = 1.48, 7.52 Hz, IH) , 7.95 (app t, J = i.61 Hz, IH) , 7.80 (app dr, J = 6.72, 8.59 Hz, IH) 7.69-7.60 (m, 2H), 7.48 (br s, IH) , 7.35 (ddd, J = 2.55, 9.53, 10.61 Hz, IH) , 7.247.19 (m, IH) , 6.97 (s, IH) , 5.49 (s, 2H) , 4.71 (AB q, J;a : 15.04 Hz, 2H) , 1.98 (s, 3H) . ES-HRMS m/z 463.0883 (M+H calcd for C 22 HIvCIF 2 N 2 Os requires 463.0867). Example 707 BF 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- { [2- (methylthio)pyrimidin-5-yl]methyl}pyridin-2 (iH)-one Step i. Preparation of methyl 2-(methylthio)pyrimidine-5carboxylate :N A solution of the sodium salt of 3,3-dimethoxy-2methoxycarbonylpropen-l-ol (5.0g, 25 mmol) , 2-methyl-2thiopseudourea sulfate (3.5g, 25 mmol) in anhydrous methanol (25 mL) was refluxed for 3 hours under anhydrous conditions. The reaction mixture was cooled and diluted with ethy! acetate. The reaction mixture was filtered and the residue was washed with ethyl acetate. The filtrate was concentrated and the residue was purified by flash chromatography (silica gel) using 25% ethyl acetate in hexane to afford the desired product (3.5g, 75%) as a white powder. ZH-NMR (d -DMSO, 400 MHz) 6 9.0 (s, 2H), 3.92 (s, 3H), 2.58 (s, 3H) ; ES-HRMS m/z 185.041 (M+H CTHsN 2 0 2 S requires 185.0379). Step 2. Preparation of [2- (methylthio)pyrimidin-5-yl]methanol To a cold suspension of methyl 2-(methylthio)pyrimidine5-carboxylate (1.74g, 9.4 mmol) in dichloromethane (20 mL, 70° C) was added DIBAL (20.8 mL, 20 mmol) dropwise via an addition funnel. The mixture was stirred under nitrogen at - 70° C for 1 hour and then at -50° C for 3 hours. The reaction was diluted with dichloromethane (50 mL) and quenched with a suspension of sodium sulfate decahydrate (10g) in water (50 mL) . The slurry was filtered through celite and the filtrate was concentrated. The residue was purified by flash chromatography (silica gel) using 100% ethyl acetate to afford the desired compound (0.7813 g, 39%) as a yellow solid. IHNMR ((CD 3 OD, 400 MHz) 6 8.53 (s, 2H), 4.56 (s, 2H), 2.54 (s, 3H) ; ES-HRMS m/z 157.0409 (M+H C 6 HsN 2 0S requires 157.0430). Step 3. Preparation of 5-(chloromethyl)-2- (methylthio)pyrimidine To a cold solution of [2-(methylthio)pyrimidin-5yl]methanol (0.7813g, 5.0 mmol) in anhydrous dichloromethane (i0 mL, 0° C) was added triethylamine (0.836 mL, 8.2 mmol) followed by the addition of methanesulfonyl chloride (0.465mL, 6.0 mmol). The reaction mixture stirred at 0° C under a nitrogen atmosphere for 30 minutes then at room temperature for 3.5 hours. The reaction was quenched with sodium bicarbonate (5%, i00 mL)) and extracted with dichloromethane (50 mL) . The organic extracts were concentrated and the residue was purified by flash chromatography (silica gel) using 15% ethyl acetate in hexane to afford the desired compound (0.720 g, 82%) as a white solid. IH-NMR ((CD 3 OD, 400 MHz) 6 8.60 (s, 2H), 4.64 (s, 2H) , 2.54 (s, 3H) ; ES-HRMS m!z 175.0106 (M+H C 6 HTN 2 CIS requires 175.0091). Step 4. Preparation of 3-bromo-4- [(2,4-difluorobenzyl)oxy]-6methyl-l-{ [2- (methylthio)pyrimidin-5-yl]methy]}pyridin-2 (IH) - one To a solution of 5-(chloromethyl)-2- (methylthio)pyrimidine (0.62g, 3.56 mmol) in anhdrous DMF (i0 mL) was added KBr (0.424, 3.56 mmol). After the suspension stirred at room temperature for 30 minutes, 2-bromo-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one (l.05g, 3.19 mmol) was added followed by NaH (0.102g, 4.25 mmol). The reaction mixture stirred at 70° C under a nitrogen atmosphere for 3.5 hours. The solvent was disti!led and the residue was washed with water and extracted with ethyl acetate. The organic extracts were concentrated and the residue was purified by reverse phase HPLC using a 10-90% acetonitrile/water (30 minute gradient) at a 70mL/min flow rate to afford the desired TFA salt (0.32 g, 15%) as a white powder. The TFA compound was washed with sodium bicarbonate (5%) and extracted with dichloromethane. The organic extract was concentrated to afford the desired compound (0.295g, 18 %) 468.0174/470.0156 (M+H C 19 HI 6 N O 2 F BrS requires 468.0187/470.0168) . Example 708 O O Br 3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-l- { [2- (methylsul fonyl) pyrimidin5-yl] methyl } pyridin2 (IH) -one To a solution of 3-bromo-4- [ (2,4-difluorobenzyl)oxy]-6methyl-l- { [2 - (methylthio) pyrimidine-5-yl] methyl}pyridin-2 (IH) - one (example 707) (0.26g, 0.55 mmol) in acetonitrile: water (4:1 v/v, i0 mL) was added MMPP (0.549g, I.I mmol) . The reaction stirred at room temperature for 30 hours. The reaction mixture was diluted with ethyl acetate and filtered. The filtrate was concentrated and the residue was purified by reverse phase HPLC using a 10-90% acetonitrile/water (30 minute gradient) at a 70mL/min flow rate to afford the desired TFA salt of the title copmound (0.13 g, 38%) as a white powder. IH-NMR ((CD 3 OD, 400 MHz) 6 8.86 (s, 2H), 7.62 (q, IH, J= 8Hz), 7.02 (m, 2H), 6.56 (s, IH), 5.48 (s, 2H), 5.31 (s, 2H), 3.34 (s, 3H), 2.49 (s, 2H); ES-HRMS m/z 500.0109/502.0066 (M+H C 19 HI N 3 0 4 F 2 BrS requires 500.0086/502.0067) . Example 709 Ethyl 2-({ [3-bromo-l-(5-{ [(2-hydroxyethyl)amino]carbonyl}-2methylphenyl)-6-methyl-2-oxo-l,2-dihydropyridin-4yl]oxy}methyl)-5-fluorobenzylcarbamate To a cooled (-10°C) solution of 3- [3-bromo-4- [ (2- { [ (ethoxycarbonyl) amino] methyl } -4fluorobenzyl) oxy] -6 -methyl2-oxopyridin-l(2H)-yl]-4-methylbenzoic acid (0.25 g, 0.46 mmol) and 4-methylmorpholine (0.06 mL, 0.55mmol) in DMF was added isobutyl chloroformate (0.07 mL, 0.55 mmol). The colorless solution gradually turned dark brown. After 30 min, ethaolamine (0.04 mL, 0.69 mmol) was added and the solution warmed to RT. After lh, solvent was removed and the crude product was purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHCO] (20 mL) and extracted in DCM (3 x 15 mL) . The organic extracts were dried over Na 2 SO 4 , filtered, and concentrated to a white solid, dried in vacuo (0.09 g, 33%). IH NMR (CD 3 OD/ 400MHz) 6 7.88 (m, IH), 7.61 (s, IH), 7.53 (m, 2H), 7.13 (m, IH), 7.05 (m, IH), 6.68 (s, IH), 5.40 (s, 2H), 4.43 (s, 2H), 4.07 (q, 2H, J = 7.2 Hz), 3.68 (t, 2H, J = 5.6 Hz), 3.48 (t, 2H, J = 5.6 Hz), 2.09 (s, 3H), 2.00 (s, 3H), 1.22 (t, 3H , J = 7.2 Hz) . ESHRMS m/z 590.1266 and 592.1254 (M+H calculated for C 2 vH 30 BrFN O requires 590.1297 and 592.1281). Example 710 3-bromo-4-[(2,4-difluorobenzyl)oxy]-!-[5-(iH-imidazo!-2-yl)-2methylphenyl]-6-methylpyridin-2(iH)-one trifluoroacetate An oven-dried flask was alternately evacuated and flushed with argon. Toluene (2.18 mL) and trimethyl aluminum (1.25 mL, 2.51 mmol) were added sequentially and the solution cooled to -5°C. Ethylene diamine (0.17 mL, 2.51 mmol) was added dropwise. Methyl 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6methyl-2-oxopyridin-l(2H)-yl]-4-methylbenzoate (0.75 g, 1.57 mmol) was added portionwise to the cooled solution. The reaction mixture was then refluxed at II0°C for 4h. The solution was cooled and water (0.7 mL), DCM (2.2 mL), and MeOH (2.2 mL) were added. The solution was refluxed for 15 min following this addition and then dried over Na 2 SO 4 , filtered, and concentrated. The residue was dissolved in EtOAc (20 mL), refluxed 15 min, dried over Na 2 S0 4 , filtered, and concentrated. The crude product was purified by preparatory HPLC. The product was isolated by freeze-drying and evaporation of the solvent to give a white solid, dried in vacuo (0.30 g, 31%). IH NMR (CD 3 OD/ 400MHz) 6 7.88 (m, IH), 7.71 (d, IH, J = 8.0 Hz), 7.64 (m, 2H), 7.05 (m, 2H), 6.70 (s, IH), 5.37 (s, 2H), 4.09 (s, 4H) , 2.16 (s, 3H) , 2.01 (s, 3H) . ESHRMS m/z 488.0750 and 490.0774 (M+H calculated for C 23 H 21 BrF 2 N 0 2 requires 488.0780 and 490.0762). Example 711 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l-[5-(5-hydroxy-lHpyrazol-3-yl)-2-methylpheny!]-6-methylpyridin-2(iH)-one Step i: Preparation of ethyl 3-{3-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyI-2-oxopyridin-l(2H)-yl]-4methylphenyl}-3-oxopropanoate. 0 Br OEI In an oven-dried round bottom flask, 3- [3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-!(2H)-yl]-4methylbenzoic acid (see Example 487) (0.75 g, 1.62 mmol), DCM (2.00 mL), and oxalyl chloride (0.97 mL, 1.94 mmol) were combined under argon. DMF (3-5 drops) was added to aid in dissolution. Stirred at RT overnight. Solvent was removed and the crude acid ch!oride was coevaporated with DCM (3-5 mL 3) and dried in vacuo to give an orange solid. In a separate oven-dried flask, in an argon atmosphere, a solution of monoethyl malonate (0.38 mL, 3.23 mmol) in THF (3.00 mL) was cooled to -78°C. Isopropyl magnesium chloride (3.23 mL, 6.46 mmol) was added dropwise. The solution was stirred for 30 min at -78°C. The acid chloride prepared as described above was added dropwise as a solution in THF. The reaction was warmed to RT. After 30 min, the reaction was cooled (0°C) and 10% citric acid (5.0 mL) added. The crude product was extracted in EtOAc, washed with 5% NaHCO dried over Na 2 S0 4 , filtered, and concentrated to a crude brown oil. Recrystallization from DCM and hexane. Filtered a beige solid, dried in vacuo (0.41 g, 47%) . i}{ NMR (CD 3 OD/ 400MHz) 6 8.02 (m, IH), 7.79 (s, IH) , 7.65 (m, 2H), 7.05 (t, 2H, J = 9.2 Hz), 6.66 (s, IH) , 5.36 (s, 2H) , 4.16 (q, 2H, J = 7.2 Hz) , 2.1! (s, 3H) , 2.07 (s, 2H) , 1.99 (s, 3H), 1.23 (t, 3H, J = 7.2 Hz) . ESHP MS m/z 534.0744 and 536.0746 (M+H calculated for C 2 sH 23 BrF 2 NOs requires 534.0722 and 536.0706) . Step 2: Preparation of the title compound To a mixture of ethyl 3-{3-[3-bromo-4-[(2,4difluorobenzyl) oxy] -6-methyl-2-oxopyridin-I (2H) -yl] -4methylphenyl}-3-oxopropanoate (from Step i) (0.20 g, 0.37 mmol) in EtOH (5.00 mL) was added hydrazine hydrate (0.01 mL, 0.41 mmol) . The reaction mixture was heated at 60°C with a condensere. After lh, additional hydrazine hydrate (0.01 mL) was added. After 2h, acetic acid (2 drops) was added. At 4h, additional hydrazine was added (0.! mL) . At 5h, the reaction appeared to be complete. Left in fridge overnight. Precipitate filtered, washed with hexane, found to be product, a white solid (0.I0 g, 54%). IH NMR (CD 3 OD/ 400MHz) 6 7.66 (m, 2H), 7.45 (m, 2H), 7.05 (t, 2H, J = 9.6 Hz), 6.65 (s, IH), 5.36 (s, 2H), 2.04 (s, 3H), 2.02 (s, 3H) . ESHRMS m/z 502.0552 and 504.0569 (M+H calculated for C 23 HIgBrF 2 N 3 0 3 requires 502.0572 and 504.0555) . Example 712 3-bromo-4- [ (2,4-difluorobenzyl)oxy] -i- [5- (5-hydroxyisoxazol-3yl) -2-methylphenyl] -6-methylpyridin-2 (IH) -one A solution of ethyl 3-{3- [3-bromo-4-[(2,4-difluorobenzyl)oxy]- 6-methyl-2-oxopyridin-l(2H)-yl]-4-methylphenyl}-3oxopropanoate (0.20 g, 0.37 mmol), triethylamine (0.06 L%, 0.41 mmol), and hydroxylamine hydrochloride (0.03 g, 0.41 mmol) in EtOH (3.00 mL) was heated overnight at 60°C with a condenser. Additional triethylamine (0.06 mL) and hydroxylamine hydrochloride (0.03 g) were added. After 2.5h, the additions of triethylamine and hydroxylamine hydrochloride were repeated. After lh, the reaction was concentrated and purified by preparatory HPLC. The product was isolated by freeze-drying and evaporation of the solvent to give a white solid. Dissolved solid in DCM. Upon addition of 5% NaHCO solution became a milky emulsion. Added additional DCM and some brine. Organic extracts were dried over Na 2 SO 4 , filtered, and concentrated to a pink solid, dried in vacuo (120 mg, 64%). IH NMR (CD 3 OD/ 400MHz) 6 7.66 (m, 2H), 7.44 (m, 2H), 7.04 (t, 2H, J = 8.8 Hz) , 6.64 (s, IH) , 5.36 (s, 2H), 2.04 (s, 3H) , 2.01 (s, 3H) . ESHRMS m/z 503.0415 and 505.0402 (M+H calculated for C 23 HIsBrF 2 N O 4 requires 503.0413 and 505.0395). Example 713 3- [4- { [2- ( { [ (cyclopropylamino) carbonyl] amino}methy!) -4fluorobenzyl] oxy}-6-methyl-2-oxopyridin-i (2H) -yl] -N, 4dimethylbenzamide To a cooled (-15°C) solution of 3-[4-{ [2- ( { [ (cyclopropylamino) carbonyl] amino}methyl) -4fluorobenzyl ] oxy} - 6-methyl-2-oxopyridin1 (2H) -yl ] -4- methylbenzoic acid (see Example 651) (0.30 g, 0.63 mmol) and isobutyl chloroformate (0.I0 mL, 0.75 mmol) in DMF (3.00 mL) was added 4-methylmorpholine (0.08mL, 0.75 mmol) . The solution instantly turned yellow and was dark brown within minutes. After 20 min, methylamine (0.47 mL of 2.0M solution in THF, 0.94 mmol) was added. The reaction was carried out at RT. After 2.5h, a catalytic amount of DMAP and additional methylamine (0.47 mL, 0.94 mmol) were added. After an additional 2.5h, the reaction was concentrated to a dark red oil. The crude product was purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHCO 3 (20 mL) and extracted in DCM (3 x 15 mL) . The organic extracts were dried over Na 2 SO 4 , filtered, and concentrated to an off-white solid, dried in vacuo (0.06 g, 19%). H NMR (CD 3 OD/ 400MHz) 6 7.85 (m, IH), 7.58 (s, IH), 7.48 (m, 2H), 7.14 (m, IH) , 7.02 (m, IH) , 6.23 (s, IH) , 6.09 (s, IH) , 5.20 (s, 2H), 4.45 (s, 2H), 2.90 (s, 3H), 2.49 (m, IH) , 2.11 (s, 3H), 1.91 (s, 3H), 0.71 (m, 2H), 0.48 (m, 2H) . ESHRMS m/z 493.2260 (M+H calculated for C 27 H 30 N 4 0 4 F requires 493.2246). Example 714 O O\ Methyl 4-{ [4- [ (2,4-difluorobenzyl)oxy]-2-oxoquinolin-l(2H)- yl] methyl }benzoate Step i: Preparation of 3-bromo-4-[(2,4difluorobenzyl) oxy] quinolin-2 (IH) -one . NH To a room temperature solution of 4-hydroxy-l,2- dihydroquinolin-2-one (500 m 9, 3.10 mmol) in CH 2 C1 2 (I0.0 mL) was added portion-wise solid N-bromosuccinimide (551.5 mg, 3.10 mmol). The reaction was stirred vigorously for 1.0 h, followed by the sequential addition of K 2 CO 3 (540 mg, 3.90 mmol), DMF (4.0 mL), and 2,4 difluorobenzyl bromide (0.430 mL, 3.30 mmol) . The resulting suspension was stirred for 4.5 hours until complete formation of desired product was seen by LCMS analysis. The reaction was then diluted with ethyl acetate (400 mL) and brine washed (3 X 200 mL) . The resulting organic extract was Na 2 S0 4 dried, filtered, and concentrated in vacuo to a residue that was subjected to Si0 2 chromatography with ethyl acetate/hexanes/methanol (60:35:5) to furnish a 5.25 (s, 2H); LC/MS C-18 column, tr = 2.64 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 366 (M+H). ES-HRMS m/z 365.9967 (M+H calcd for C 16 HIIBrF 2 NO 2 requires 365.9936). Step 2: Preparation of methyl 4-{ [3-bromo-4- [(2,4difluorobenzyi)oxy] -2-oxoquinolin-l(2H) - yl]methyl}benzoate O O To a room temperature solution of 3-bromo-4-[(2,4difluorobenzyl)oxy]quinolin-2 (IH) -one (400 rag, 1.09 retool) in THF (4.5 mL) was added portion-wise solid sodium hydride (95 oil-free, 60.0 mg, 2.49 mmol) . The reaction was vigorously stirred for 30 minutes followed by addition of methyl-4- (bromomethyl)-benzoate (400 mg, 1.75 retool). This resulting suspension was then heated to 60 °C for 12.0 hours. The resulting solution was then treated with saturated aqueous ammonium chloride (400 mL) and extracted with ethyl acetate X 300 mL). The resulting organic extracts were Na 2 SO dried, filtered, and concentrated in vacuo to a residue that was subjected to SiO 2 chromatography with ethyl acetate/hexanes (60:40) to furnish a solid (396 rag, 71%). IH NMR (400 MHz, C-18 column, tr = 3.46 minutes (5 to 95% acetonitri!e/water over 5 minutes at i ml/min with detection 254 nm, at 50°C) . ESMS m/z 514 (M+H) . ES-HRMS m/z 514.0451 (M+H calcd for C 25 H!gBrF 2 NO 4 requires 514.0460) . Step 3: Preparation of the title compound In a 25 mL round bottom flask was added, at room temperature, a solution of methyl 4-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-2- oxoquznolin-l(2H)- yl]methyl}benzoate (step 2) (120 mg, 0.233 mmol) in MeOH (3.0 mL). Next, a combination of Pd on carbon (I0 % Pd, weight by weight 50 % water, i00 mg, 0.047 mmol) and Pd(OAc) (15 mg, 0.067 mmol) was added to the reaction vessel that purged with argon and then fitted with a septum. The vessel was then equipped with a 2.0 L hydrogen balloon (c.a. psi). The resulting suspension was allowed to stir of 12.0 hours and was then directly applied to SiO 2 chromatography using ethyl acetate/ hexanes (3:7) to furnish the desired title compound as a solid (52 mg, 51%). IH NMR (300 MHz, CDCI 3 ) 6 8.05-7.98 (m, 3H), 7.55 (app q, J = 8.3 Hz, IH), 7.48 (app t, J = 7.5 Hz, IH), 7.30 (d, J = 8.0 Hz 2H), 7.19 (app q, J = 8.5, 2H), 7.05-6.90 (m, 2H), 6.28 (s, IH), 5.60 (s, 2H), 5.26 (s, 2H), 3.91 (s, 3H) ; LC/MS C-18 column, tr = 3.71 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 436 (M+H). ES-HRMS m/z 436.1371 (M+H calcd for C 2 sH 0 BrF 2 NO 4 requires 436.1355). Example 715 5- { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2-oxopyridin1 (2H) -yl]methyl}-2-furamide Step i: Preparation of 5-{ [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]methyl}-2furoic acid . To a room temperature solution of methyl 5-{ [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]methyl}-2furoate (Example 660) (608 g, 1.30 mmol) in THF (8.0 mL) was added dropwise an aqueous solution of sodium hydroxide (3.0 M, 0.50 mL, 1.50 mmol). The reaction was then heated to 60 °C for 12.0 hours. The resulting suspension was then diluted with 500 mL of ethyl acetate and neutralized with an aqueous solution of hydrochloric acid (i.0 N, 1.5 mL, I0 mmol). The resulting biphasic solution was then concentrated in vacuo to a volume of 50 mL. At this time a white solid began to form and the resulting solid suspension was allowed to sit until precipitation appeared to stop (approximately 1.0 hour). The precipitate was collected and dried in vacuo (I.0 mm Hg) to furnish the solid acid as an intermediate (500 rag, 85 %). IH C-18 column, tr = 2.38 minutes (5 to 95% acetonitrile/water over 5 minutes at ! ml/min with detection 254 nm, at 50°C) . ESMS m/z 454 (M+H) . ES-HRMS m/z 454.0070 (M+H calcd for CI 9 HIsBrF 2 NOs requires 454.0096) . Step 2: Preparation of the title compound. To a room temperature suspension of 5-{ [3-bromo-4- [(2,4- difluorobenzyl)oxy] ÷6-methyl-2-oxopyridin-I (2H) -yl]methyl}-2furoic acid (500 mg, !.!0 mmol) in THF (6.0 mL) was added 2ch!oro-4,6 dimethoxy-l,3,5 triazine (307 rag, 1.75 retool) and Nmethyl morpholine (NMM, 184 mg, 1.82 mmol) sequentially. The resulting solution was matured for 2 hours and then a saturated aqueous solution of ammonium hydroxide (0.70 mL) was added. The resulting suspension was allowed to continue for 1 additional hour. The reaction mixture was diluted with 400 mL of brine and extracted with ethyl acetate (3 X 400 mL) . The organic extracts were separated, Na 2 S0 4 dried, and concentrated in vacua and the resulting residue was subjected to SiO 2 chromatography with ethyl acetate/hexanes/methanol (57:38:5) to provide the title compound (370 g, 74 %). IH NMR (300 MHz, d 4-MeOH) 6 7.64 (app q, J = 8.1 Hz 0 IH), 7.10-7.00 (m, 3H), 6.53 (s, IH) , 6.52 (d, J = 3.4 Hz, IH) , 5.43 (s, 2}{), 5.32 (s, 2H), 2.61 (s, 3}{); LC/MS C-18 column, tr = 2.15 minutes (5 to 95% acetonitrile/water over 5 minutes at i ml/min with detection 254 nm, at 50°C). ES-MS m/z 453 (M+H) . ES-HRMS m/z 453.0249 (M+H calcd for C 19 HI BrF 2 N 2 0 4 requires 453.0256). Example 716 5- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-2-oxopyridin1 (2H) -yl ] -2furamide Step i: Preparation of methyl 5-(4-hydroxy-6-methyl-2oxopyridin1 (2H) -yl) -2furoate HO To a room temperature solution of methyl-2-amino-5-furoate (4.85 g, 34.4 mmol) in 1,4 dioxane (28.0 mL) was added 5-(1hydroxy-3-oxobutylidene)-2,2-dimethyl-l,3-dioxane-4,6-dione (8.16 g, 44.3 mmol) . The reaction was stirred vigorously and heated quickly (within 8 minutes) to an internal temperature of 98 °C. Upon reaching temperature, the reaction was maintained for 1.0 hour. At this time, the reaction was cooled to room temperature rapidly using an ice-bath and methane sulfonic acid (3.30 g, 34.4 mmol) was added. The reaction mixture was once again brought to an internal temperature of approximately i00 °C. After 1.0 hour the reaction was diluted with I0 mL of toluene and allowed to cool to room temperature on its own accord. A solid formed after 3.0 hours that was collected and subsequently recrystallized from methanol/ ethyl acetate (i:i). The developing crystals were allowed to form and stand for 12.0 hours prior to collection to furnish the desired product as a solid (3.78 g, 44 %). IH NMR (400 MHz, d - minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 250 (M+H) . ES-HRMS m/z 250.0696 (M+H calcd for C 12 H 12 NO 5 requires 250.0710). Step 2: Preparation of methyl 5- [3-bromo-4- [(2,4difluorobenzyl) oxy] - 6-methyl-2-oxopyridin1 (2H) -yl] -2furoate O O To a room temperature solution of methyl 5-(4-hydroxy-6methyl-2-oxopyridin-l(2H)-yl)-2-furoate (step I) (3.19 g, 12.8 mmol) in DMF (14 mL) was added portion-wise solid Nbromosuccinimide (2.29 g, 12.9 mmol) . The reaction was stirred vigorously for 1.0 h, followed by the sequential'addition of K 2 C0 3 (1.88 g, 13.6 mmol), DMF (4.0 niL), and 2,4 difluorobenzyl bromide (2.00 mL, 15.55 mmol). The resulting suspension was stirred for 9.0 hours until complete formation of desired product was seen by LCMS analysis. The reaction was then diluted with saturated brine (300 mL) and extracted with ethyl acetate (3 X 300 mL) . The resulting organic extracts were Na 2 SO 4 dried, filtered, and concentrated in vacuo to a residue that was subjected to SiO 2 chromatography with a gradient elution using ethyl acetate/hexanes (40:60 to 60:40) to furnish a solid (3.20 rag, 55 %). IH N-MR (400 MHz, dv-DMF) 6 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 454 (M+H) . ES-HRMS m/z 454.0117 (M+H calcd for C gHIsBrF 2 N 2 Os requires 454.0096) . Step 3: 5- [3-bromo-4- [ (2,4-dif!uorobenzyl)oxy]-6-methyl-2oxopyridin-I (2H)-yl]-2-furoic acid O O To a room temperature solution of methyl 5-[3-bromo-4-[(2,4difluorobenzyl) oxy] - 6-methyl-2-oxopyridin1 (2H) -yl ] -2furoate (step 2) (3.00 g, 6.61 mmol) in THF (20 mL) was added dropwise an aqueous solution of sodium hydroxide (3.0 M, 4.00 mL, 12.0 mmol) . The reaction was then heated to 60 °C for 12.0 hours. The resulting suspension was then diluted with 800 mL of ethyl acetate and neutralized with an aqueous solution of hydrochloric acid (3.0 N, 4.0 mL, 12 retool) . The resulting biphasic solution was then concentrated in vacuo to a volume of 90 mL. At this time a white solid began to form and the resulting solid suspension was allowed to sit until precipitation appeared to stop (approximately 1.0 hour). The precipitate was collected and dried in vacuo (I.0 mm Hg) to furnish the solid acid as an intermediate (2.27 g, 78 %). IH NMR (400 MHz, dT-DMF) 6 7.79 (app q, J = 8.0 Hz, IH), 7.32 (t, J = 9.2 Hz, IH), 7.20 (app t, J = 7.4 Hz, IH), 6.88 (app d, J = 2.5 Hz, IH), 6.74 (s, IH), 6.51 (d, J = 2.5 Hz, IH), 5.44 (s, 2H), 2.10 (s, 3H) ; LC/MS C-18 column, tr = 2.77 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 440 (M+H) . ES-HRMS m/z 439.9959 (M+H calcd for CIsHnBrF 2 NOs requires 439.9940). Step 4: Preparation of the title compound. To a room temperature suspension of 5- [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-2-furoic acid (i.00 g, 2.27 mmol) in THF (8.0 mL) was added 2-chloro- 4,6 dimethoxy-l,3,5 triazine (610 mg, 3.47 mmol) and N-methyl morpholine (NMM, 368 mg, 3.62 mmol) sequentially. The resulting solution was matured for 2 hours and then a saturated aqueous solution of ammonium hydroxide (1.5 mL) was added. The resulting suspension was allowed to continue for 1 additional hour. The reaction mixture was diluted with 800 mL of brine and extracted with ethyl acetate (3 X 600 mL). The organic extracts were separated, Na 2 S0 4 dried, and concentrated in vacuo and the resulting residue was subjected to Si0 2 chromatography with ethyl acetate/hexanes/methanol (57:38:5) to provide the title compound (710 mg, 71%) . H NMR (400 MHz, dv-DMF) 6 8.07 (s, IH), 7.79 (app q, J = 8.6 Hz, IH), 7.50 (br s, IH), 7.32 (app dt, J = i0.i, 2.2 Hz, IH), 7.30 (app dd, J = 8.0, 3.3 Hz, IH), 7.20 (app dt, J = 8.6, 2.0 Hz, IH), 6.81 (s, IH), 6.79 (d, J = 3.4 Hz, IH), 5.47 (s, 2H), 2.14 (s, 3H) ; LC/MS C-18 column, tr = 2.60 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 439 (M+H). ES-HRMS m/z 439.0088 (M+H calcd for C 18 HI 4 BrF 2 N 2 0 4 requires 439.0010). Example 717 I- [3,5-his (hydroxymethyl) phenyl] -3-bromo-4- [ (2,4di f luorobenzyl ) oxy] - 6 -methylpyridin2 (IH) -one Step I: Preparation of dimethyl 5-(4-hydroxy-6-methyl-2oxopyridin-l(2H)-yl)isophthalate Dimethyl 5-aminoisophthalate (24.45 g, 117 mmol) was dissolved in 500 ml toluene and heated to reflux. 5-(l-hydroxy-3oxobutylidene)-2,2-dimethyl-l,3-dioxane-4,6-dione (40.0 g, 175.3 mmol) was added and refluxed for 15 minutes. The reaction was evaporated. 500 ml of acetonitrile and ptoluenesulphonic acid (22.25 g, 117 mmol) was added and refluxed for 1 hour. The reaction was allowed to cool to room temperature and stand over night. The resulting precipitate was filtered, washed three times with 250 ml water and 250 ml acetonitrile and dried in vacuo to give a tan solid (18.85 g, 51% yield). H NMR (300 MHz, DMSO-d 6 ] 6 10.70 (br s, IH), 8.47 (t, J = 1.54 Hz, IH), 7.99 (d, J = 1.47 Hz, 2H) , 5.90 (d, J = 1.61 Hz, IH), 5.55 (d, J = 2.42 Hz, IH), 3.87 (s, 6H), 1.82 (s, 3H); LC/MS, tr = 1.79 minutes (5 to 95% acetonitrile/water over 5 minutes at I ml/min, at 254 nm, at 50°C), ES-MS m/z 318 (M+H) . ES-HRMS m/z 318.0994 (M+H caicd for C: H= NO requires 318.0972). Step 2 : Preparation of dimethyl 5- (3-bromo-4-hydroxy-6methyl-2-oxopyridin-i (2H) -yl) isophthalate Br oN O/ 0 -0 I Dimethyl 5- (4-hydroxy-6-methyl-2-oxopyridin-i (2H) - yl)isophthalate (from Step !) (18.0 g, 56.7 mmol) was stirred at room temperature with N-Bromosuccin±mide (10.6 g, 59.6 mmol) in 35 ml of N,N-dimethylformamide and 180 ml of methylene chloride. After stirring for 1 hour, a white precipitate had formed. The precipitate was filtered, washed with acetonitrile and dried in vacuo to give a white solid (11.55 g, 51%). IH NMR (400 MHz, DMSO-d ) 6 11.49 (br s, IH), 8.49 (t, J = 1.24 Hz, IH), 8 06 (d, J = 1.47 Hz, 2H), 6.07 (s, IH), 3.88 (s, 6H), 1.82 (s, 3H) ; LC/MS, tr = 1.81 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 396 (M+H). ES-HRMS m/z 396.0102 (M+H calcd for CIGHIsBrNO requires 396.0077). Step 3: Preparation of dimethyl 5-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]isophthalate . Dimethyl 5- (3-bromo-4-hydroxy6-methyl-2-oxopyridin1 (2H) - yl)isophthalate (from Step 2) (11.3 g, 28.5 mmol) was stirred briskly with 2,4-difluorobenzylbromide (3.66 ml, 28.5 mmol) and K 2 CO (5.91 g, 42.8 retool) in 50 ml of N,N-dimethylformamide at room temperature for 3 hours. The reaction was then poured into IL of cold water and the resulting precipitate was filtered, washed with water and diethyl ether, and dried in vacuo to yield a white solid (13.8 g, 93%). H NMR (400 MHz, DMSO-d 6) 6 8.51 (t, J = 1.60 Hz, IH) , 8.12, (d, J = 1.60 Hz, 2H) , 7.67 (app q, J = 7.92 Hz, IH), 7.34 (app dt, J -- 9.94, 2.19 Hz, IH) , 7.17 (dt, J = 8.53, 2.11 Hz, IH) , 6.68 (s, IH) , 5.33 (s, 2H) , 3.88 (s, 6H) , 1.93 (s, 3H) ; LC/MS, tr = 2.77 minutes (5 to 95% acetonitrile/water over 5 minutes at ! ml/min, at 254 nm, at 50°C), ES-MS m/z 522 (M+H) . ES-HR/MS m/z 522 .0335 (M+H calcd for C 23 HIgBrF 2 N0 6 requires 522.0358). Step 4: Preparation of 5-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]isophthalic acid O Dimethyl 5- [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2- oxopyridin-l(2H)-yl]isophthalate (from Step 3) (5.0 g, 9.57 mmol) was stirred at room temperature with 2.5 N NaOH (15.3 ml, 38.3 mmol) in 30 m! of 5:1 THF/water for 1 hour. The reaction was then acidified with 1 N HCI and the resulting precipitate was filtered, washed with water, and dried in vacuo to yield a white solid (4.48 g, 95%). IH NMR (400 MHz, (s, IH), 5.32 (s, 2H), 1.94 (s, 3H); LC/MS, tr = 2.27 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C) , ES-MS m/z 494 (M+H) . ES-HRMS m/z 494.0054 (M+H calcd for C 21 H sBrF NO 6 requires 494.0045). Step 5: Preparation of the title compound 5-[3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)- yl]isophthalic acid (from Step 4 above) (500 mg, i.01 mmol) was added to a solution of IM borane-dimethylsulfide complex in tetrahydrofuran (9.0 ml, 9.00 mmol) in 2.5 ml tetrahydrofuran at 0°C. The reaction was allowed to warm to room temperature while stirring. After stirring overnight, more IM borane-dimethylsulfide complex in tetrahydrofuran (0.60 ml, 0.60 mmol) was added and stirring at room temperature. After 4 hours, ice chips were added to quench the reaction. The reaction was extracted 2 times with ethyl acetate and the combined organic layers were washed with brine, dried over MgS0 4 and evaporated. The resulting solid was washed with acetonitrile and diethyl ether and dried in vacuo to give a white solid (281 mg, 60%). IH NMR (400 MHz, DMSO-d ) 6 7.66 (app q, J = 7.92 Hz, IH), 7.35 (s, IH), 7.33 (dt, J = 9.40, 2.24 Hz, IH), 7.16 (dt, J = 8.52, 1.88 Hz, IH), 6.99 (s, 2H) , 6.62 (s, IH) , 5.31 (s, 2H) , 5.27 (br s, 2H) , 4.51 (s, 4H) , 1.93 (s, 3H) ; LC/MS, tr = 2.19 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 466 (M+H). ES-HRMS m/z 466.0454 (M+H calcd for C 21 HIgBrF 2 NO 4 requires 466.0460). Example 718 5- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-2-oxopyridin1 (2H) -yl] isophthalamide 5- [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin_ l(2H)-yl]isophthalic acid (Example 717, step 4) (500 rag, 1.01 mmo!l was dissolved in 4 ml of tetrahydrofuran. 0.5M ammonia in 1,4-dioxane (12.12 ml, 6.06 mmol) was added, followed, in order, by EDCI (494 mg, 2.53 mmol) , l-hydroxybenzotriazole (342 mg, 2.53 mmol) and triethylamine (563 i, 4.04 mmol) . The reaction was stirred at room temperature overnight. The reaction evaporated and water was used to triturate the product. The resulting solid was filtered and washed with water, acetonitrile, ethyl acetate and diethyl ether, and dried in vacuo to give a white solid (202 rag, 41%). IH NMR (400 MHz, DMSO-d 6 ) 6 8.45 (s, IH), 8.08 (br s, 2H) , 7.86, (d, J = 1.34 Hz, 2H), 7.67 (app q, J = 7.92 Hz, IH), 7.55 (br s, 2H) , 7.33 (dr, J = 9.94, 2.18 Hz, IH) , 7.17 (dt, J = 8.59, 1.92 Hz, IH), 6.70 (s, IH), 5.34 (s, 2H}, 1.96 (s, 3H) ; LC/MS, tr = 2.10 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 492 (M+H). ES-HRMS m/z 492.0381 (M+H calcd for C 21 HIvBrF 2 N 3 0 4 requires 492.0365). Example 719 difluorobenzyl)oxy]-6methylpyridin-2(!H)-one Dimethy! 5-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]isophthalate (Example 717, step 3) (500 mg, 0.96 mmol) was added dro pwise to a solution of 3M MeMgBr in diethyl ether (1.6 ml, 4.79 mmol) in 15 ml of tetrahydrofuran at -5°C and stirred at -5°C. The reaction turned red. After 2.5 hours, the reaction was quenched with a saturated NH 4 CI solution and extracted 2 times with ethyl acetate. The combined organic layers were washed with NaHCO 3 solution and brine, dried over MgSO and evaporated. The resulting solid was washed with diethyl ether and dried in vacuo to give a white solid (329 rag, 66%). IH NMR (400 MHz, DMSO-d 6 ) 6 7.69 - 7.63 (m, 2H), 7.33 (dt, J = 9.87, 2.41 Hz, IH), 7.16 (dt, J = 8.46, 1.75 Hz, IH) , 7.07 (d, J = 1.48 Hz, 2H) , 6.61 (s, IH) , 5.32 (s, 2H), 5.06 (s, 2H), 1.89 (s, 3H), 1.41 (s, 12H); LC/MS, tr = 2.45 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 522 (M+H) . ES-HRMS m/z 522.1098 (M+H calcd for C 2 sH 2 ?BrF NO 4 requires 522.1086). Example 720 (hydroxymet hyl ) phenyl ] - 6 - me t hylpyridin - 2 (IH) -one 4- [3-bromo-4- [ (2,4-difluorobenzyl)oxy] -6-methyl-2-oxopyridinl(2H)-yl]benzoic acid (Example 203) (500 mg, i.ii mmol) was added to a solution of 2M borane-dimethylsulfide complex in tetrahydrofuran (3.33 ml, 6.66 mmol) in 2.5 ml tetrahydrofuran at 0°C. The reaction was allowed to warm to room temperature while stirring. After 2.5 hours, ice chips were added to quench the reaction. The resulting precipitate was filtered, washed with diethyl ether and dried in vacuo to give a white solid (160 rag, 33%). IH NMR (400 MHz, DMSO-d 6 ) 6 7.66 (app q, J = 7.88 Hz, IH), 7.42 (d, J = 8.19 Hz, 2H), 7.33 (dt, J = 9.87, 2.06 Hz, IH) , 7.197.14 (m, 3H), 6.62 (s, IH), 5.31 (s, 2H), 5.30 (s, IH), 4.54 (d, J = 5.24, 2H), 1.92 (s, 3H) ; LC/MS, tr = 2.36 minutes (5 to 95% acetonitrile/water over minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 436 (M+H) . ES-HRMS m/z 436.0374 (M+H calcd for C 20 HIvBrF 2 N0 3 requires 436. 0354) . Example 721 methylethyl ) phenyl ] -6-methylpyridin-2 (IH) -one Methyl-4-[3-bromo-4-[(2s4-difluorobenzyl)oxy]-6-methyl-2oxopyridin-l(2H)-yl]benzoate (Example 202) (500 mg, 1.08 mmol) was added dropwise to a solution of 3M MeMgBr in diethyl ether (0.90 ml, 2.69 mmol) in 15 ml of tetrahydrofuran at -5°C and stirred at -5°C. After 2.75 hours, more 3M MeMgBr in diethyl ether (0.45 ml, 1.35 mmol) was added and stirred at -5°C. After 4 hours, the reaction was quenched with a saturated NH 4 CI solution and extracted 2 times with ethyl acetate. The combined organic layers were washed with NaHCO 3 solution and brine, dried over MgSO 4 and evaporated. The resulting solid was washed with diethyl ether and dried in vacuo to give a white solid (268 rag, 53%). IH NMR (400 MHz, DMSO-d 6 ) 6 7.66 (app q, J = 7.92 Hz, IH) , 7.57 (d, J = 8.46 Hz, 2H) , 7.33 (dt, J = 9.87, 2.11 Hz, IH), 7.16 (dt, J = 8.59, 2.24 Hz, IH), 7.14 (d, J = 8.63 Hz, 2H), 6.62 (s, IH), 5.31 (s, 2H), 5.12 (s, IH) , 1.91 (s, 3H), 1.44 (s, 6H) ; LC/MS, tr = 2.54 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50°C), ES-MS m/z 464 (M+H) . ES-HRMS m/z 464.0604 (M+H calcd for C 22 H 21 BrF 2 NO requires 464.0667). Example 722 l-(5-amino-2-fluorophenyl)-3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one hydrochloride Step 1 Preparation of tert-butyl 3- [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4fluorophenylcarbamate .Br O F O N H A solution of the compound of Example 519 (4.3 g, 9.2 mmol) in tert-butanol (50 mL) was flushed with nitrogen. Diphenyl phosphoryl azide (2 mL, 9.2 mmol) and triethyl amine (1.3 mL, 9.2 mmol) were added. After heating at 90 C for 20 h, the reaction mixture was concentrated in vacuo. The residue was diluted with methylene chloride and was washed sequentially with aqueous ammonium chloride and aqueous NaHCO]. The organic layer was concentrated in vacuo; the resulting solids were suspended in acetonitrile and filtered to give the title compound (2.9 g, 58%). IH NMR (400 MHz, CD 3 OD) 6 7.64 (q, J CODED) 6 -111.53 (IF) , -115.93 (I F) , -132.58 ppm. ES-HRMS m/z 540.0822 (M+H calcd for C 24 H 23 BrF 3 N 2 0 4 requires 540.0820). Step 2 Preparation of l-(5-amino-2-fluorophenyl)-3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(iH)-one hydrochloride F .Br :O HCI NH 2 The product of Step i, (2.9 g, 5.3 mmol) was dissolved in tetrahydrofuran (75 mL) and 6N HCI (i0 mL). The reaction mixture was heated at 60 C for 18h and was concentrated in vacuo to give the final product (1.89 g, 75%) . IH N 4R (a00 MHz, CD 3 OD) 6 7.64 (q, J = 8.4 and 15.2 Hz, IH), 7.56 (m, 2H), 7.46 (m, IH) , 7.05 (m, 2H) , 6.69 (s, IH), 5.37 (s, 2H), 2.10 (s, 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6 -111.37 (IF) , -115.86 (I F) , -123.16 ppm. ES-HRMS m/z 440.0334 (M+H calcd for C 19 HIsBrF 3 N 2 0 2 requires 440.0295) . Example 723 .Br 'O O .OH N H N- { 3- [3-bromo-4- [ (2,4-difluorobenzyl) oxy] - 6-methyl-2oxopyridin1 (2H) -yl] -4 - fluorophenyl } -2-hydroxyacetamide Step 1 Preparation of 2-({3-[3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4fluorophenyl}amino)-2-oxoethyl acetate .Br "O F O O A solution of the compound of Example 722 (0.5 g, 1.05 mmol) in tetrahydrofuran (20 mL) was treated with triethyl amine (0.3 mL, 2.1 mmol) and acetoxy acetylchloride (0.12 mL, 1.15 mmol). After stirring at room temperature for 2h, the reaction was complete. The reaction mixture was poured into saturated aqueous ammonium chloride. The solids were filtered off and were washed with water and diethyl ether. Title product was isolated as a white solid (0.32 g, 58%). IH NMR (400 MHz, CD 3 OD) 6 7.65 (m, 3H), 7.32 (t, J = 8.4 Hz, IH), 7.04 (t, J = 8.4 Hz, 2H), 6.64 (s, IH), 5.35 (s, 2H), 4.68 (s, 2H), 2.15 (s, 3H), 2.10 (s 0 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6111.56 (IF), -i15.99 (i F), -129.48 (IF) ppm. LC/MS, tr = 5.35 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 540 (M+H) . Step 2 Preparation of N-{3-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4fluorophenyl}-2-hydroxyacetamide The product of Step i, (0.I g, 0.18 mmol) was suspended in tetrahydrofuran (i0 mL), methanol (2 mL), and 2.5 N NaOH (i mL) . After stirring at room temperature for i hour, the reaction was complete and the organics were removed in vacuo. The aqueous layer was acidified to pHI with 6N HCl, the solids were suspended in water, filtered, and washed with diethyl ether. The title compound was obtained as a white powder (56.2 rag, 61%). IH NMR (400 MHz, CD 3 OD) 6 7.75 (dq, 2.9, 4.8 and 9.2 Hz, IH), 7.71 (dd, J = 2.4 and 6.8 Hz, IH), 7.64 (q, J = 8 and 14.8 Hz, IH), 7.32 (t, J = 9.6 Hz, IH), 7.04 (t, J = 8.8 Hz, 2H) , 6.64 (s, IH) , 5.36 (s, 2}{), 4.10 2H) , 2.10 (s, 3H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6 -iii.54 (IF), -115.99 (i F), -129.71 (IF) ppm. LC/MS, tr = 5.04 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50°C). ES-MS m/z 498 (M+H). Example 724 { [3-bromo-4- [ (2,4-difluorobenzyl) oxy] 6-methyl-2oxopyridin1 (2}{) -yl ] -4 - fluoropheny! } -2 - hydroxy-2met hyl propanamide Step 1 Preparation of 2-({3- [3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4fluorophenyl}amino)-l,l-dimethyl-2-oxoethyl acetate F O A solution of the compound of Example 722 (0.5 g, 1.05 mmol) in tetrahydrofuran (20 mL) was treated with triethyl amine (0.3 mL, 2.1 mmol) and l-chlorocarbonyl-l-methylethy/ acetate (0.16 mL, 1.15 mmol) . After stirring at room temperature for 2h, the reaction was complete. The reaction mixture was poured into saturated aqueous ammonium chloride. The solids were filtered off and were washed with water and diethyl ether. The compound of Step 1 was isolated as a white solid (0.23 g, 39%). IH NMR (400 MHz, CODED) 6 7.64 (m, 2H), 7.54 (dd, J = 2.8 and 6.8 Hz, IH), 7.30 (t, J = 9.2 Hz, IH), 7.04 (t, J = 9.2 Hz, 2H), 6.64 (s, IH), 5.35 (s, 2H), 2.11 (s, 3H), 2.08 (s, 3H), 1.61 (s, 6H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6111.57 (IF), -116.00 (i F), -129.56 (IF) ppm. LC/MS, tr = 5.65 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 568 (M+H). Step 2 Preparation of N-{3-[3-bromo-4- [(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-4fluorophenyl}-2-hydroxy-2-methylpropanamide The product of Step 1 0.I g, 0.17mmol) was suspended in tetrahydrofuran (I0 mL), methanol (2 mL), and 2.5 N NaOH (i mL) . After stirring at room temperature for 1 hour, the reaction was complete and the organics were removed in vacuo. The aqueous layer was acidified to pHi with 6N HCl, the solids were suspended in water, filtered, and washed with diethyl ether. The title compound was obtained as a white powder (56 rag, 61%). H NMR (400 MHz, CD 3 OD) 6 7.75 (dq, 2.8, 4.4 and 9.2 Hz, IH) , 7.69 (dd, J = 2.8 and 6.8 Hz, IH), 7.64 (q, J = 8 and 14.8 Hz, IH), 7.31 (t, J = 9.2 Hz, IH) , 7.04 (t, J = 8.4 Hz, 2H), 6.64 (s, IH) , 5.35 (s, 2H), 2.10 3H) , 1.43 (s, 6H) ppm. 19 F NMR (400 MHz, CD 3 OD) 6-111.55 (IF), -115.95 (i F), -129.80 (IF) ppm. LC/MS, tr = 5.34 minutes (5 to 95% acetonitrile/water over 8 minutes at 1 ml/min with detection 254 nm, at 50°C) . ES-MS m/z 526 (M+H). Example 725 4_[ 3_br 0 m 0-4-[(2,4-diflu 0 r 0 benzyl)oxy]-6-methyl-2-oxopyridinl(2H)-yl]-3-fluoro-N,N-dimethylbenzamide Step 1 Preparation of 4- [3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-yl]-3fluorobenzoic acid F .Br F " 0 F Compound of Example 604 (4.1 g, 8.5mmol) was suspended in tetrahydrofuran (30 mL), methanol (15 mL), water (15 mL) and 2.5 N NaOH (6.8 mL, 17 mmol)). After stirring at room temperature for 2 hour, the reaction was complete and the organics were removed. The aqueous layer was acidified to pH 1 with 3N HCI, the solids were suspended in water, filtered, and washed with diethyl ether. The title compound was obtained as a white powder and used without further purification (4.4 g) . zH NMR (400 MHz, CD 3 OD) 6 8.00 (dd, J 123.35 (IF) ppm. ES-HRMS m/z 468.9987 (M+H ca!cd for C 20 H 4 BrF 3 NO 4 requires 469.0086). Step 2 Preparation of 4-[3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methyl-2-oxopyridin-l(2H)-v!]-3-f!uoroF .Br F N,N-dimethylbenzamide A solution of the product of Step 1 (0.5 g, 1.07 mmol) in N,Ndimethyl formamide was cooled to 0 C. Iso-butyl chloroformate (0.14 mL, 1.07 mmol) and N-methyl morpholine (0.12 mL, 1.07 mmol) were added. After 20 minutes, N,N-dimethylamine (2.0 M, i.i mL, 2.14 mmol) was added and the reaction mixture was warmed to room temperature over 18 h. The reaction mixture was partitioned between ethyl acetate and saturated aqueous NaHCO 3 . The organics were washed with brine and concentrated in vacuo. The resulting semi-solid was treated with ethyl acetate and acetone to precipitate the title compound (90 mg, 17%). IH NMR (400 MHz, dmso-d 6 ) 6 7.67 (q, J = B and 14.8 Hz, IH) , 7.52 (m, 2H), 7.35 (m, 2H), 7.18 (td, J = 2.8 and 8.8 Hz, IH) , 6.73 (s, IH), 5.34 (s, 2H), 2.98 (s, 3H), 2.91 (s, 3H) , 2.00 (s, 3H) ppm. 19 F NMR (400 MHz, dmso-d 6 ) 6 -109.50 (IF), -113.63 (i F) , -122.09 (IF) ppm. ES-HRMS m/z 496.0570 (M+H calcd for CnH gBrF 3 N 2 0 3 requires 496.0558). Example 726 dihydro-iH-indol-5-yl)methyl]-6-methylpyridin-2(iH)-one A I0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with compound of Example 633 (180 mg, 0.43 mmol), acetoxyacetyl chloride (51 L, 0.47 mmol), triethylamine (119 L, 0.86 mmol) and tetrahydrofuran (3.0 mL) After stirring at 25° C for 20 min the reaction was completed by LC-MS. NaOH (2.5M, 2.24 mmol, 1.0 mL) and MeOH (2.0mL) was added and stirred for 20 min to give the title compound. The compound precipitated out cf solution. The precipitated was filtered and washed with water and diethyl ether to obtain the title compound (130 mg, 64%) as a white solid. IH NMR (400 MHz, (DMSO) 6 7.9 (d, J = 8.2, IH), 7.6 (q, J = 8.5 and 6.9 Hz, IH) 7.3 (t, J = 8.7 Hz, IH), 7.1 (t, J = 7.9 Hz, IH), 6.9 (s, 2H), 6.5 (s, IH), 5.25 (s, 2H), 4.1 (d, J = 5.5 Hz, 2H), 3.9 (t, J = 8.6 Hz, 2H) , 3.42 (t, J = 5.4 Hz, IH) , 3.35 (t, J = 4.8 Hz, IH) , 3.2 (t, J = 8.5 Hz, 2H) , 2.3 (s, 3H) ppm. ES-HRMS m/z 475.1220 (M+H calcd for C 24 HnCIF 2 N 2 0 4 requires 475.1231) . Example 727 methy!propanoyl)-2,3-dihydro-!H-indol-5-yl]methyl}-6methylpyridin-2(IH)-one A i0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with compound of Example 633 (200 mg, 0.48 mmol), l-chlorocarbonyl-l-methylethyl acetate (104.3 L, 0.72 mmol), triethylamine (133 L, 0.96 mmol) and tetrahydrofuran (4.0 mL). After stirring at 25° C for 20 min the reaction was completed by LC-MS. NaOH (2.5M, 2.24 mmol, 1.5 mL) and MeOH (2.0mL) was added and stirred for 20 min to give the title compound. The compound precipitated out of solution. The precipitate was filtered and washed with water and diethyl ether to obtain a white solid (240 rag, 99%). IH NMR (400 MHz, (DMSO) 6 8.0 (d, J = 8.3, IH) , 7.6 (q, J = 8.6 and 6.9 Hz, IH), 7.3 (td, J = 2.5 and 7.8 Hz, IH), 7.1 (td, J = 1.75 and 6.7 Hz, IH), 6.95 (s, IH), 6.89 (d, J = 8.5 Hz, IH), 6.58 (s, IH) , 5.25 (s, 2H) , 4.3 (t, J = 8.3 Hz, 2H), 3.42 (t, J = 5.4 Hz, IH), 3.35 (t, J = 5.2 Hz, IH), 3.0 (t, J = 8.2 Hz, 2H), 2.3 (s, 3H), 1.3 (s, 6H) ppm. ES-HRMS m/z 503.1561 (M+H calcd for C 2 H 2 ClF 2 N 2 0 4 requires 503.1544). Example 728 O 3-chloro-4- [ (2,4-difluorobenzyl)oxy] -i-{ [i- (methoxyacetyl) - 2,3 - dihydroIHindol -5 -yl ] methyl } - 6 -met hylpyridin - 2 (IH) -one A i0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with compound of Example 633 (200 mg, 0.48 mmol), methoxyacety! chloride (66 L, 0.72 mmol), triethylamine (134 L, 0.96 mmol) and tetrahydrofuran (4.0 mL) After stirring at 25° C for 20 min the reaction was completed by LC-MS. The compound precipitated out of solution. The precipitate was filtered and washed with water and diethyl ether to obtain a white solid (195 mg, 83%). IH NMR (400 MHz, (DMSO) 6 8.0 (d, J = 8.0, IH), 7.6 (q, J = 8.6 and 6.7 Hz, IH) 7.3 (td, J = 2.4 and 6.7 Hz, IH), 7.1 (td, J = 1.88 and 6.6 Hz, IH), 6.9 (s, 2H), 6.58 (s, IH), 5.25 (s, 2H) , 4.15 (s, 2H) , 3.9 (t, J = 8.3 Hz, 2H), 3.45 (m, IH), 3.4 (m, !H) , 3.32 (s, 3H), 3.0 (t, J = 8.5 Hz, 2H), 2.3 (s, 3H) ppm. ES-HRMS m/z 489.1387 (M+H calcd for C 2 sH 24 CIF 2 N 2 0 4 requires 489.1387). Example 729 O 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] -6-methyl-2oxopyridin-l(2H)-yl]methyl)-N,N-dimethylindoline-l-carboxamide A i0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with compound of Example 633 (200 mg, 0.48 mmol), dimethylcarbamyl chloride (66 L, 0.72 mmol), triethylamine (133 L, 0.96 mmol) and tetrahydrofuran (4.0 mL) After stirring at 25° C for 5 min the reaction was completed by LC-MS. The compound precipitated out of solution. The pr-ecipitate was filtered and washed with water and diethyl ether to obtain a white solid (198 mg, 85%). zH NMR (400 MHz, (DMSO) 7.6 (q, J = 7.4 Hz, IH), 7.3 (t, J = 8.9 Hz, IH) , 7.1 (t, J = 8.5 Hz, 2H), 6.93 (s, IH), 6.86 (s, !H), 6.58 (s, IH), 5.25 (s, 2H), 3.9 (t, J = 8.2 Hz, 2H), 3.45 (m, IH), 3.4 (m, IH) , 2.9 (t, J = 8.3 Hz, 2H}, 2.8 (s, 6H), 2.3 (s, 3H) ppm. ES-HRMS m/z 488.1548 (M+H calcd for C 2 sH 24 CIF 2 N 2 0 4 requires 488.1547). Example 730 3-chloro-4- [ (2,4-difluorobenzyl) oxy] -i- [ (!-glycoloyl-2,3dihydro-IHindol-5-yl) methyl] pyridin-2 (IH) -one A i0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with compound of Example 88 (200 mg, 0.5 mmol), acetoxyacetyl chloride (59 NL, 0.55 mmol), triethylamine (140 NL, 1.0 mmol) and tetrahydrofuran (3.0 mL). After stirring at 25° C for 20 min the reaction was completed by LC-MS. NaOH (2.5M, 2.24 mmol, 1.0 mL) and MeOH (2.0mL) was added and stirred for 20 min to give the title compound. The compound precipitated out of solution. The precipitated was filtered and washed with water and diethyl ether to obtain the title compound (200 mg, 83%) as a white solid. IH NMR (400 MHz, J = 7.9 Hz, 2H), 3.1 (t, J = 7.9 Hz, 2H) ppm. ES-HRMS m/z 461.1088 (M+H calcd fo[- C 23 H 20 C!F 2 N 2 0 4 requires 461.!074). Example 731 Preparation of 3-chloro-4- [ (2,4-difluorobenzyl)oxy]-l- [ (lglycol oyl-2,3 -dihydroIHindol5-yl) methy! ] pyridin2 (1H) -one A l0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with compound of Example 88 (200 mg, 0.50 mmol), l-chlorocarbonyl-l-methylethyl acetate (80 L, 0.55 mmol), triethylamine (140 L, 1.0 mmol) and tetrahydrofuran (4.0 mL) . After stirring at 25° C for 20 min the reaction was completed by LC-MS. NaOH (2.5M, 2.24 mmol, 1.5 mL) and MeOH (2.0mL) was added and stirred for 20 min to give the title compound. The compound precipitated out of solution. The precipitated was filtered and washed with water and diethyl ether to obtain the title compound (136 mg, 55%) a white solid. IH NMR (400 MHz, (DMSO) 6 7.98 (d, J = 8.1, IH), 7.9 (d, J = 7.8 Hz, IH), 7.6 (q, J = 8.6 and 6.6 Hz, IH), 7.3 (m, IH), 7.1 (m, 2H), 6.56 (d, J =7.8 Hz, IH), 5.25 (s, 2H),5.0 (s, 2H), 4.3 (t, J = 7.8 Hz, 2H), 3.0 (t, J = 7.9 Hz, 2H), 1.3 (s, 6H) ppm. ES-HRMS m/z 489.1376 (M+H calcd for C 25 H 24 CIF 2 N 2 0 4 requires 489.1387). Example 732 3-chloro-4- [ (2,4-difluorobenzyl) oxy] - i- { [i- (methoxyacety!) - 2,3 -dihydroIHindo] - S-yl ] methyl }pyridin2 (iH) -one A i0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the compound of Example 88 (200 mg, 0.5 mmol), methoxyacetyl chloride (69 L, 0.75 mmol), triethylamine (139 L, 1.0 mmol) and tetrahydrofuran (4.0 mL). After stirring at 25° C for 20 min the reaction was completed by LC-MS. The compound precipitated out of solution. The precipitate was filtered and washed with water and diethyl ether to obtain a white solid (195 rag, 83%). IH NMR (400 MHz, (DMSO) 6 7.98 (d, J = 8.2, iH) , 7.9 (d, J = 7.7 Hz, IH) , 7.6 (d, J = 8.5 Hz, IH) , 7.3 (t, J = 9.6 Hz, IH) , 7.1 (m, 9H) , 6.56 (d, J --7.8 Hz, IH) , 5.25 (s, 2H) ,S.! (s, 2H) , 4.1 (s, 2H), 3.98 (t, J = 7.9 Hz, 2H), 3.33 (s, 3H), 3.0 (t, J = 7.9 Hz, 2H) ppm. ES-HRMS m/z 461.1088 (M+H calcd for C 23 H 20 CIF 2 N 2 0 requires 461. 1074) . Example 733 I F O 5- { [3-chloro-4- [ (2,4-difluorobenzyl) oxy] 2-oxopyridin1 (2H) - yl ] methyl } -N, Ndime t hyl indol ine - 1 - carboxamide A I0 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the compound of Example 88 (200 mg, 0.5 mmol), dimethylcarbamyl chloride (69 L, 0.75 mmo!), triethylamine (139 L, 1.0 mmol) and tetrahydrofuran (4.0 niL). After stirring at 25° C for 5 min the reaction was completed by LC-MS. The compound precipitated out of solution. The precipitate was filtered and washed with water and diethyl ether to obtain a white solid (188 mg, 58%). iN N-MR (400 MHz, (DMSO) 6 7.9 (d, J = 8.i, IH), 7.6 (q, J = 8.6 and 6.6 Hz, IH), 7.3 (t, J = 9.3 Hz, IH), 7.1 (m, 3H), 6.8 (d, J =8.0 Hz, IH), 6.5 (d, J = 7.8 Hz, H), 5.25 (s, 2H),5.0 (s, 2H), 3.7 (t, J = 8.6 Hz, 2H), 2.9(t, J = 7.9 Hz, 2H), 2.8 (s, 6H) ppm. ES-HRMS m/z 474.1387 (M+H calcd for C 24 H 23 CIF 2 N 3 0 3 requires 474.1391) . BIOLOGICAL EVALUATION p38 Kinase Assay Cloning of human p38a: The coding region of the human p38a cDNA was obtained by PCR-amplification from RNA isolated from the human monocyte cell line THP.I. First strand CDNA was synthesized from total RNA as follows: 2 g of RNA was annealed to i00 ng of random hexamer primers in a i0 i reaction by heating to 70° C. for I0 minutes followed by 2 minutes on ice. cDNA was then synthesized by adding 1 i of RNAsin (Promega, Madison Wis.), 2 i of 50 n 4 dNTP's, 4 i of 5X buffer, 2 I of 100 mM DTT and 1 i (200 U) of Superscript II AMV reverse transcriptase. Random primer, dNTP's and Superscript II TM reagents were all purchased from Life-Technologies, Gaithersburg, Mass. The reaction was incubated at 42° C. for 1 hour. Amplification of p38 cDNA was performed by aliquoting 5 I of the reverse transcriptase reaction into a i00 I PCR reaction containing the following: 80 i dH.sub.2 O, 2 i 50 mM dNTP's, 1 i each of forward and reverse primers (50 pmol/ l) , i0 i of 10X buffer and i Expand TM polymerase (Boehringer Mannheim). The PCR primers incorporated Bam HI sites onto the 5' and 3' end of the amplified fragment, and were purchased from Genosys. The sequences of the forward and reverse primers were 5' GATCGAGGATTCATGTCTCAGGAGAGGCCCA-3' and 5'GATCGAGGATTCTCAGGACTCCATCTCTTC-3' respectively. The PCR amplification was carried out in a DNA Thermal Cycler (Perkin Elmer) by repeating 30 cycles of 94° C. for 1 minute, 60° C. for 1 minute and 68° C. for 2 minutes. After amplification, excess primers and unincorporated dNTP's were removed from the amplified fragment with a Wizard TM PCR prep (Promega) and digested with Bam HI (New England Biolabs) . The Bam HI digested fragment was ligated into BamHI digested pGEX 2T plasmid DNA (PharmaciaBiotech) using T-4 DNA ligase (New England Biolabs) as described by T. Maniatis, Molecular Cloning: A Laboratory Manual, 2nd ed. (1989). The ligation reaction was transformed into chemically competent E. coli DHIOB cells purchased from Life-Technologies following the manufacturer's instructions. Plasmid DNA was isolated from the resulting bacterial colonies using a Promega wizard TM miniprep kit. Plasmids containing the appropriate Bam HI fragment were sequenced in a DNA Thermal Cycler (Perkin Elmer) with Prism TM (Applied Biosystems Inc.). cDNA clones were identified that coded for both human p38a isoforms (Lee et al. Nature 372, 739). One of the clones that contained the cDNA for p38a-2 (CSB-2) inserted in the cloning site of PGEX 2T, 3' of the GST coding region was designated pMON 35802. The sequence obtained for this clone is an exact match of the cDNA clone reported by Lee et al. This expression plasmid allows for the producLion of a GST-p38a fusion protein. Expression of human p38a GST/p38a fusion protein w as expressed from the plasmid pMON 35802 in E. coli, stain DHIOB (Life Technologies, GibcoBRL). Overnight cultures were grown in Curia Broth (LB) containing i00 mg/ml ampici!lin. The next day, 500 ml of fresh LB was inoculated with I0 ml of overnight culture, and grown in a 2 liter flask at 37° C. with constant shaking until the culture reached an absorbance of 0.8 at 600 nm. Expression of the fusion protein was induced by addition of isopropyl bD-thiogalactosidase (IPTG) to a final concentration of 0.05 mM. The cultures were shaken for three hours at room temperature, and the cells were harvested by centrifugation. The cell pellets were stored frozen until protein purification. Purification of P38 Kinase-alpha All chemicals were from Sigma Chemical Co. unless noted. Twenty grams of E. coli cell pellet collected from five 1 L shake flask fermentations was resuspended in a volume of PBS (140 mM NaCI, 2.7 mM KCI, i0 mM Na.sub.2 HPO.sub.4, 1.8 mM KH.sub.2 PO.sub.4, pH 7.3) up to 200 mlo The cell suspension was adjusted to 5 mM DTT with 2 M DTT and then split equally into five 50 ml Falcon conical tubes. The cells were sonnicated (Ultrasonics model W375) with a 1 cm probe for 3.times.l minutes (pulsed) on ice. Lysed cell material was removed by centrifugation (12,000 x g, 15 minutes) and the clarified supernatant applied to glutathione-sepharose resin (Pharmacia). Glutathione-Sepharose Affinity Chromatography Twelve ml of a 50% glutathione sepharose-PBS suspension was added to 200 ml clarified supernatant and incubated batchwise for 30 minutes at room temperature. The resin was collected by centrifugation (600.times.g, 5 min) and washed with 2.times.150 ml PBS/I% Triton X-100, followed by 4.times.40 ml PBS. To cleave the p38 kinase from the GST-p38 fusion protein, the glutathione-sepharose resin was resusmended in 6 ml PBS containing 250 units thrombin protease (Pharmacia, specific activity >7500 units/mg) and mixed gently for 4 hours at room temperature. The glutathione-sepharose resin was removed by centrifugation (600.times.g, 5 min) and washed 2.times.6 ml with PBS. The PBS wash fractions and digest supernatant containing p38 kinase protein were pooled and adjusted to 0.3 mM PMSF. Mono Q Anion Exchange Chromatography The thrombin-cleaved p38 kinase was further purified by FPLC-anion exchange chromatography. Thrombin-cleaved sample was diluted 2-fold with Buffer A (25 mM HEPES, pH 7.5, 25 mM beta-g 1 ycer 0 ph 0 sphate, 2 mM DTT, 5% glycerol) and injected onto a Mono Q HR I0/i0 (Pharmacia) anion exchange column equilibrated with Buffer A. The column was eluted with a 160 ml 0.i M-0.6 M NaCl/Buffer A gradient (2 ml/minute flowrate) . The p38 kinase peak eluting at 200 mM NaCI was collected and concentrated to 3-4 ml with a Filtron i0 concentrator (Filtron Corp.). Sephacryl SI00 Gel Filtration Chromatography The concentrated Mono Qp38 kinase purified sample was purified by gel filtration chromatography (Pharmacia HiPrep 26/60 Sephacryl SI00 column equilibrated with Buffer B (50 mM HEPES, pH 7.5, 50 mM NaCI, 2 rnM DTT, 5% glycerol)). Protein was eluted from the column with Buffer B at a 0.5 ml/minute flowrate and protein was detected by absorbance at 280 nm. Fractions containing p38 kinase (detected by SDSpolyacrylamide gel electrophoresis) were pooled and frozen at -80° C. Typical purified protein yields from 5 L E. co!i shake flasks fermentations were 35 mg p38 kinase. In Vitro Assay The ability of compounds to inhibit human p38 kinase alpha was evaluated using two in vitro assay methods. In the first method, activated human p38 kinase alpha phosphorylates a biotinylated substrate, PHAS-I (ph0sphorylated heat and acid stable protein-insulin inducible), in the presence of gamma ]2P-ATP (32P-ATP) . PHAS-I was biotinylated prior to the assay and provides a means of capturing the substrate, which is phosphorylated during the assay, p38 Kinase was activated by MKK6. Compounds were tested in i0 fold serial dilutions over the range of I00 M to 0.001 M using 1% DMSO. Each concentration of inhibitor was tested in triplicate. All reactions were carried out in 96 well polypropylene plates. Each reaction well contained 25 mM HERPES pH 7.5, I0 mM magnesium acetate and 50 M unlabeled ATP. Activation of p38 was required to achieve sufficient signal in the assay. Biotinylated PHAS-I was used at 1-2 #g per 50 #i reaction volume, with a final concentration of 1.5 #M. Activated human p38 kinase alpha was used at i g per 50 #i reaction volume representing a final concentration of 0.3 #M. Gamma 32p-ATP was used to follow the phosphorylation of PHAS-I. 32p-ATP has a specific activity of 3000 Ci/mmol and was used at 1.2 Ci per i reaction volume. The reaction proceeded either for one hour or overnight at 30° C. Following incubation, 20 i of reaction mixture was transferred to a high capacity streptavidin coated filter plate (SAM-streptavidin-matrix, Promega) prewetted with phosphate buffered saline. The transferred reaction mix was allowed to contact the streptavidin membrane of the Promega plate for 1-2 minutes. Following capture of biotinylated PHASI with np incorporated, each well was washed to remove unincorporated 2P-ATP three times with 2M NaCI, three washes of 2M NaC! with 1% phosphoric, three washes of distilled water and finally a single wash of 95% ethanol. Filter plates were air-dried and 20 I of scintillant was added. The plates were sealed and counted. A second assay format was also employed that is based on p38 kinase alpha induced phosphorylation of EGFRP (epidermal growth factor receptor peptide, a 21 mer) in the presence 33p_ ATP. Compounds were tested in i0 fold serial dilutions over the range of i00 M to 0.001 #M in 1% DMSO. Each concentration of inhibitor was tested in triplicate. Compounds were evaluated in 50 #i reaction volumes in the presence of 25 mM Hepes pH 7.5, i0 mM magnesium acetate, 4% glycerol, 0.4% bovine serum albumin, 0.4mM DTT, 50 M unlabeled ATP, 25 g EGFRP (200 M), and 0.05 Ci 33p-ATP. Reactions were initiated by addition of 0.09 #g of activated, purified human GST-p38 kinase alpha. Activation was carried out using GST-MKK6 (5:I,p38:MKK6) for one hour at 30° C. in the presence of 50 #M ATP. Following incubation for 60 minutes at room temperature, the reaction was stopped by addition of 150 i of AG l.times.8 resin in 900 mM sodium formate buffer, pH 3.0 (i volume resin to 2 volumes buffer). The mixture was mixed three times with pipetting and the resin was allowed to settle. A total of i of clarified solution head volume was transferred from the reaction wells to Microlite-2 plates. 150 #i of Microscint was then added to each well of the Microlite plate, and the plate was sealed, mixed, and counted. Representative compounds that exibit ICs 0 values between 1 and 25 M (p38 alpha kinase assay) are: Example Nos. 20, 22, 23, 39, 43, 44, 48, 50, 52, 53, 55, 57, 58, 62, 92, 115, 118, 136, 139, 141, 142, 149, 156, 157, 169, 174, 219 220, 244 245, 387, 288, 289, 291, 292 293, 294, 295, 296 298, 297 300, 301, 302 304, 305, 309, 310, 311, 323, 360, 394, 403, 414, 415, 416, 418, 420, 444 447, 449, 451, 452 471, 485 486, 496, 498, 499, 503, 506 561, 569, 574, 575 and 576. Representatve compounds that exibit ICs 0 values between and i00 NM (p38 alpha kinase assay) are: Example Nos. I, 25, 33, 35, 37, 42, 45, 47, 49, 119, 204, 308, 558, 560, 564, 565, 566, 568 and 577. Representatve compounds that exibit ICs 0 values less than 1 MM (p38 alpha kinase assay) are: Example Nos. 6, 14, 8, 17, i0, 15, 4, 117, 161, 162, 165, 170, 171, 172, 173 176, 179 217, 218, 219, 220, 221, 223, 225, 230, 231, 234, 235, 272 273 275, 276, 278, 280, 282, 286, 285, 290, 312, 313, 314 315 316, 317, 318, 320, 321, 322, 364, 366, 400, 402, 405 421 422, 423, 446, 448, 450, 458, 466, 467, 468, 469, 470 481 482, 483, 484, 487, 489, 492, 493, 494, 495, 504, 521 522, 523 557, 587, 589, 590, 591, 597, 609, 610, 613, 629, 642, and 643. Representatve compounds that exibit ICs 0 values greater than i00 MM (p38 alpha kinase assay) are: Example Nos. 3, Ii, 38, 56, 116, 121, 237, 236, 413, 497 and 578. TNF Cell Assays Method of Isolation of Human Peripheral Blood Mononuclear Cells: Human whole blood was collected in Vacutainer tubes containing EDTA as an anticoagulant. A blood sample (7 ml) was carefully layered over 5 ml PMN Cell Isolation Medium (Robbins Scientific) in a 15 ml round bottom centrifuge tube. The sample was centrifuged at 450-500.times.g for 30-35 minutes in a swing out rotor at room temperature. After centrifugation, the top band of cells were removed and washed 3 times with PBS w/o calcium or magnesium. The cells were centrifuged at 400 .times.g for I0 minutes at room temperature. The cells were resuspended in Macrophage Serum Free Medium (Gibco BRL) at a concentration of 2 million cells/mi. LPS Stimulation of Human PBMs PBM cells (0.i ml, 2 million/ ml) were co-incubated with 0.i ml compound (10-0.41 M, final concentration) for 1 hour in flat bottom 96 well microtiter plates. Compounds were dissolved in DMSO initially and diluted in TCM for a fina! concentration of 0.1% DMSO. LPS (Calbiochem, 20 ng/ml, final concentration) was then added at a volume of 0.010 ml. Cultures were incubated overnight at 37° C. Supernatants were then removed and tested by ELISA for TNF-a and ILl-b. Viability was analyzed using MTS. After 0.i ml supernatant was collected, 0.020 ml MTS was added to remaining 0.i ml cells. The cells were incubated at 37° C. for 2-4 hours, then the O.D. was measured at 490-650 nM. Maintenance and Differentiation of the U937 Human Histiocytic Lymphoma Cell Line U937 cells (ATCC) were propagated in RPMI 1640 containing 10% fetal bovine serum, I00 IU/ml penicillin, I00 g/ml streptomycin, and 2 mM glutamine (Gibco). Fifty million cells in i00 ml media were induced to terminal monocytic differentiation by 24 hour incubation with 20 ng/ml phorbol 12-myristate 13-acetate (Sigma). The cells were washed by centrifugation (200.times.g for 5 min) and resuspended in i00 ml fresh medium. After 24-48 hours, the cells were harvested, centrifuged, and resuspended in culture medium at 2 million cells/ml. LPS Stimulation of TNF production by U937 Cells U937 cells (0.i ml, 2 million/ml) were incubated with 0.i ml compound (0.004-50 M, final concentration) for i hour in 96 well microtiter plates. Compounds were prepared as i0 mM stock solutions in DMSO and diluted in culture medium to yield a final DMSO concentration of 0.1% in the cell assay. LPS (E coli, I00 ng/ml final concentration) was then added at a volume of 0.02 ml. After 4 hour incubation at 37° C., the amount of TNF-.alpha. released in the culture medium was quantitated by ELISA. Inhibitory potency is expressed as IC50 (#M). Rat Assay The efficacy of the novel compounds in blocking the production of TNF also was evaluated using a model based on rats challenged with LPS. Male Harlen Lewis rats [Sprague Dawley Co.] were used in this model. Each rat weighed approximately 300 g and was fasted overnight prior to testing. Compound administration was typically by oral garage (although intraperitoneal, subcutaneous and intravenous administration were also used in a few instances) 1 to 24 hours prior to the LPS challenge. Rats were administered 30 #g/kg LPS [salmonella typhosa, Sigma Co.] intravenously via the tail vein. Blood was collected via heart puncture 1 hour after the LPS challenge. Serum samples were stored at -20° C. until quantitative analysis of TNF-.alpha. by Enzyme Linked-Immuno- Sorbent Assay ("ELISA") . Additional details of the assay are set forth in Perretti, M., et al°, Br. J. Pharmacol. (1993), II0, 868-874, which is incorporated by reference in this application. Mouse Assay Mouse Model of LPS-Induced TNF Alpha Production TNF alpha was induced in 10-12 week old BALB/c female mice by tail vein injection with i00 ng lipopolysaccharide (from S. Typhosa) in 0.2 ml saline. One hour later mice were bled from the retroorbital sinus and TNF concentrations in serum from clotted blood were quantified by ELISA. Typically, peak levels of serum TNF ranged from 2-6 ng/ml one hour after LPS injection. The compounds tested were administered to fasted mice by oral gavage as a suspension in 0.2 ml of 0.5% methylcellulose and 0.025% Tween 20 in water at 1 hour or 6 hours prior to LPS injection. The 1 hour protocol allowed evaluation of compound potency at Cmax plasma levels whereas the 6 hour protocol al!owed estimation of compound duration of action. Efficacy was determined at each time point as percent inhibition of serum TNF levels relative to LPS injected mice that received vehicle only. Induction and Assessment of Collagen-Induced Arthritis in Mice Arthritis was induced in mice according to the procedure set forth in J. M. Stuart, Collagen Autoimmune Arthritis, Annual Rev. Immunol. 2:199 (1984), which is incorporated herein by reference. Specifically, arthritis was induced in 812 week old DBA/I male mice by injection of 50 g of chick type II collagen (CII) (provided by Dr. Marie Griffiths, Univ. of Utah, Salt Lake City, Utah) in complete Freund's adjuvant (Sigma) on day 0 at the base of the tail. Injection volume was I00 i. Animals were boosted on day 21 with 50 g of CII in incomplete Freund's adjuvant (I00 i volume). Animals were evaluated several times each week for signs of arthritis. Any animal with paw redness or swelling was counted as arthritic. Scoring of arthritic paws was conducted in accordance with the procedure set forth in Wooley et al., Genetic Control of Type II Collagen Induced Arthritis in Mice: Factors Influencing Disease Suspectibility and Evidence for Multiple MHC Associated Gene Control., Trans. Proc., 15:180 (1983). Scoring of severity was carried out using a score of 1-3 for each paw (maximal score of 12/mouse) . Animals displaying any redness or swelling of digits or the paw were scored as I. Gross swelling of the whole paw or deformity was scored as 2. Ankylosis of joints was scored as 3. Animals were evaluated for 8 weeks. 8-10 animals per group were used. The invention and the manner and process of making and using it, are now described in such full, clear, concise and exact terms as to enable any person skilled in the art to which it pertains, to make and use the same. It is to be understood that the foregoing describes preferred embodiments of the present invention and that modifications may be made therein without departing from the spirit or scope of the present invention as set forth in the claims. To particularly point out and distinctly claim the subject matter regarded as invention, the following claims conclude this specification.



[2]

R 3 R 1 (1) R 4 "N° '"O I R isclosed are compounds of Fonnula (I) and phannaceutically acceptable salts thereof, wherein R R 2 , R 3 , R 4 and Rs are defined herein. These compounds are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP Kinase and/or TNF activity. Pharmaceutical compositions containing the compounds, methods of preparing the compounds and methods of treatment using the compounds are also disclosed.



A compound of the Formula I d X or a pharmaceutically acceptable salt thereof, wherein L is -O-; M is -CH 2 -; X 1 and X 2 are independently selected from hydroxy(Ci-C 4 )alkyl, H, halogen, alkyl, and R 6 R 7 N-(CI-C 6 alkyl)-; R 5 is heteroaryl or heteroarylalkyl, wherein the heteroaryl and heteroaryl groups are optionally substituted with 1,2, 3, or 4 groups that are independently -C(O)NR 6 R 7 , -NR 6 R 7, hydroxy(C]-C 4 )alkyl, H, OH, halogen, haloalkyl, alkyl, R 6 R 7 N-(C 1 -C 6 alkyl)-, and -CO 2 -(C 1 -C 6 )alkyl; wherein R 6 and R 7 are independently at each occurrence H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy C 1-C 6 alkyl, C]-C 6 alkoxycarbonyl, OH, CI-C 6 hydroxyalkyl, or C 1 -C 6 alkanoyl, wherein each of the above is unsubstituted or substituted with 1, 2, or 3 groups that are independently, OH or C 1 -C 4 alkyl; and Y, YI, Y 2 , Y 3 , and Y 4 are independently selected from H, halogen and alkyl.

2. A compound according to claim 1, wherein R 5 is a heteroaryl or heteroarylalkyl group, where each heteroaryl is pyrazolyl, imidazolyl, furanyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, imidazolyl, dihydroindolyl, dihydroisoindolyl, indolon-2-yl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, dihydroisoquinolinyl, or indolyl, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently -C(O)NR 6 R 7 , -NR 6 R 7 , hydroxy(Ci-C 4)alkyl, hydrogen, hydroxy, halogen, haloalkyl, alkyl, R 6 RTN-(CI-C 6 alkyl)-, or -CO 2 -(C 1 -C 6 )alkyl; wherein R 6 and R 7 are independently at each occurrence H, CI-C 6 alkyl, C 1 -C 6 alkoxy CI-C 6 alkyl, CI-C 6 alkoxycarbonyl, OH, CI-C 6 hydroxyalkyl, or CI-C 6 alkanoyl; wherein each of the above is unsubstituted or substituted with 1, 2, or 3 groups that are independently, OH or CI-Cn alkyl.

A compound according to claim 2, wherein Y 2, Y 4 , and Y are independently halogen; and Y and Y 3 are both hydrogen.

4. A compound according to claim 3, wherein X and X 2 are independently H, methyl, R 6 R 7 N-(C 1-C 6 alkyl)-, or hydroxy(Ci-C 4)alkyl.

5. A compound according to claim 4, wherein R 5 is pyridyl CI-C 6 alkyl, pyrimidinyl CI-C 6 alkyl, or pyrazinyl C 1 -C 6 alkyl, each of which is optionally substituted with 1, 2, or 3 groups that are independently hydroxy(C 1-C 4)alkyl, OH, halogen, (C 1 -C 4 )alkyl, -NR 6 R 7 , R 6 R 7 N-(C 1 -C 6 alkyl)-, or -C(O)NR 6 R 7.

A compound according to claim 5, wherein R 5 is of the Formula: ,wherein Z 5 is hydroxy(Ci-C 4 )alkyl, OH, halogen, (C 1 -C 4 )alkyl, -NR 6 R 7 , R 6 RTN-(CI-C 6 alkyl)-, or -C(O)NR 6 R 7 ; wherein R 6 and R 7 at each occurrence are independently H or C 1 -C 6 alkyl optionally substituted OH.

A compound according to claim 5, wherein R 5 is of the Formula: ,wherein Z 5 is hydroxy(Ci-C 4 )alkyl, OH, halogen,(Ci-C 4)alkyl, -NR 6 R 7 , R 6 R 7 N-(C 1-C 6 alkyl)-, or -C(O)NR 6 RT; wherein R 6 and R 7 at each occurrence are independently H or C1-C 6 alkyl optionally substituted with OH.

8. A compound according to claim 5, wherein Z R 5 is of the Formula: \ [ NLZ 20 , wherein Z 0 is H or methyl; and Z 20 is hydroxy(Ci-C 4 )alkyl, OH, halogen, (Ci-C 4 )alkyl, -NR 6 R 7 , R 6 RTN-(CI C 6 alkyl)-, or -C(O)NR 6 R 7 ; wherein R 6 and R 7 at each occurrence are independently H or CI-C 6 alkyl optionally substituted with OH.

A compound according to claim 5, wherein Z A.

R 5 is of the Formula: 20, wherein Z 10 is H or methyl; and Z 20 is hydroxy(C -C 4 )alkyl, OH, halogen, (C 1 -C 4 )alkyl, -NR 6 RT, R 6 R 7 N-(C 1-C 6 alkyl)-, or-C(O)NR 6 R 7 ; wherein R 6 and R 7 at each occurrence are independently H or C 1 -C 6 alkyl optionally substituted with OH.

10. A compound according to claim 5, wherein Z o R 5 is of the Formula: Z20, wherein Zlo is H or methyl; and Z 20 is hydroxy(C 1 -C 4 )alkyl, OH, halogen, (C 1 -C 4 )alkyl, -NR 6 R 7 , R 6 R 7 N (C C 6 alkyl)-, or -C(O)NR 6 R; wherein R 6 and Rv at each occurrence are independently H or C:C 6 alkyl optionally substituted with OH.

11. A compound according to claim 5, wherein Z Z 2 0 R 5 is of the Formula:, wherein Z o is H or methyl; and Z 20 is hydroxy(Ci-C 4 )alkyl, OH, halogen, (CI -C 4 )alkyl, -NR 6 R 7 , R 6 RTN-(CI-C 6 alkyl)-, or -C(O)NR 6 RT; wherein R 6 and R 7 at each occurrence are independently H or C 1 -C 6 alkyl optionally substituted with OH.

12. A compound according to claim 5, wherein Z R 5 is of the Formula: 72o, wherein Z 10 is H or methyl; and Z 20 is hydroxy(Ci-Ca)alkyl, OH, halogen, (Ci-C 4 )alkyl, -NR 6 R 7 , R 4 RvN-(C 1-C 6 alkyl)-, or -C(O)NR 6 R 7 ; wherein R 6 and R 7 at each occurrence are independently H or C -C 6 alkyl optionally substituted with OH.

13. A compound according to claim 5, wherein Z / N/N I N Z 2 0 R 5 is of the Formula:, wherein Z 10 is H or methyl; and Z 20 is hydroxy(Ci-C 4 )alkyl, OH, halogen,(C 1-C 4)alkyl, -NR 6 R 7 , R 6 R 7 N-(CI-C 6 alkyl)-, or-C(O)NR 6 R 7 ; wherein R 6 and R 7 at each occurrence are independently H or C 1-C 6 alkyl optionally substituted with OH.

14. A compound according to claim 5, wherein Z R 5 is of the Formula: Z20, wherein Z o is H or methyl; and Z 20 is hydroxy(C 1 -Ca)alkyl, OH, halogen,(Ci-C 4)alkyl, -NR 6 R 7 , R 6 R 7 N-(CI-C 6 alkyl)-, or-C(O)NR 6 R 7 ; wherein R 6 and R 7 at each occurrence are independently H or C 1-C 6 alkyl optionally substituted with OH.

15. A compound according to claim 5, wherein Z I /N Z 2 0 R 5 is of the Formula: , wherein Z 0 is H or methyl; and Z 20 is hydroxy(Ci-C 4 )alkyl, OH, halogen, (C 1 -C 4 )alkyl, -NR 6 R 7 , RrR 7 N-(C 1-C 6 alkyl)-, or -C(O)N-R 4 R 7 ; wherein R 6 and R 7 at each occurrence are independently H or C -C 6 alkyl optionally substituted with OH.

16. A pharmaceutical composition comprising a compound of any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, solvent, adjuvant or excipient.

17. A method of treating a TNF mediated disorder, a p38 kinase mediated disorder, inflammation and/or arthritis in a subject, the method comprising treating a subject having or susceptible to such disorder or condition with a compound of Formula I according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition according to claim 16.

18. A method according to claim 17 for treating or preventing inflammation; arthritis, rheumatoid arthritis, spondylarthropathies, gouty arthritis, osteoarthritis, systemic lupus erthematosus, juvenile arthritis; neuroinflammation; pain, neuropathic pain; fever; pulmonary disorders, lung inflammation, adult respiratory distress syndrome, pulmonary sarcoisosis, asthma, silicosis, chronic pulmonary inflammatory disease; cardiovascular disease, arteriosclerosis, myocardial infarction, thrombosis, congestive heart failure, cardiac reperfusion injury; cardiomyopathy; reperfusion injury; renal reperfusion injury; ischemia including stroke and brain ischemia; brain trauma; brain edema; liver disease and nephritis; gastrointestinal conditions, inflammatory bowel disease, Crohn's disease, gastritis, irritable bowel syndrome, ulcerative colitis; ulceratiuve diseases, gastric ulcers; ophthalmic diseases, retinitis, retinopathies, uveitis, ocular photophobia, acute injury to the eye tissue; ophthalmological conditions, corneal graft rejection, ocular neovascularization, retinal neovascularization, neovascularization following injury or infection, diabetic retinopathy, retrolental fibroplasias, neovascular glaucoma; diabetes; diabetic nephropathy; skin-related conditions, psoriasis, eczema, burns, dermatitis, keloid formation, scar tissue formation, angiogenic disorders; viral and bacterial infections, sepsis, septic shock, gram negative sepsis, malaria, meningitis, opportunistic infections, cachexia secondary to infection or malignancy, cachexia secondary to acquired immune deficiency syndrome (AIDS), AIDS, ARC (AIDS related complex), pneumonia, herpes virus; myalgias due to infection; influenza; endotoxic shock; toxic shock syndrome; autoimmune disease, graft vs. host reaction and allograft rejections; treatment of bone resorption diseases, osteoporosis; multiple sclerosis; disorders of the female reproductive system, endometriosis; hemaginomas, infantile hemagionmas, angiofibroma of the nasopharynx, avascular necrosis of bone; benign and malignant tumors/neoplasia, cancer, colorectai cancer, brain cancer, bone cancer, epithelial call-derived neoplasia (epithelial carcinoma), basal cell carcinoma, adenocarcinoma, gastrointestinal cancer, lip cancer, mouth cancer, esophageal cancer, small bowel cancer, stomach cancer, colon cancer, liver cancer, bladder cancer, pancreas cancer, ovarian cancer, cervical cancer, lung cancer, breast cancer, skin cancer, squamus cell and/or basal cell cancers, prostate cancer, renal cell carcinoma, and other known cancers that affect epithelial cells throughout the body; leukemia; lymphoma; systemic lupus erthrematosis (SLE); angiogenesis including neoplasia; metastasis; central nervous system disorders, central nervous system disorders having an inflammatory or apoptotic component, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal cord injury, canine B-cell lymphoma, and peripheral neuropathy.

19. A compound or pharmaceutically acceptable salt selected from 4-(4-fluorobenzyloxy)-3-bromo1 -(pyridin-4-ylmethyl)pyridin-2( 1 H)-one; 4-(4-fluorobenzyloxy)-3-bromo-l-(pyridin-3-ylmethyl)pyridin-2(1H)-one; 3-Chloro-4-(2,4-difluorobenzyloxy)- 1 -isoquinolin-5-ylmethyl1 H-pyridin-2-one; 3-Chloro-4-(2,4-difluorobenzyloxy)- 1-(1,2,3,4-tetrahydroisoquinolin°5ylmethyl)- 1H-pyridin-2-one; 3-Chloro-4-(2,4-di fluorobenzylox y)- 1 -( 1H-indol5-ylmethyl)- 1 H-pyridin-2-one; 3-Chloro-4-(2,4-difluorobenzyloxy)- 1 -(2,3-dihydro1H-indol-5-ylmethyl)- 1Hpyridin-2-one; 4-(2,4-di fluorobenzyloxy)-3-bromo1 -(pyridin-4-ylmethyl)p yridin-2(l H)-one; 4-(2,4-difluorobenzyloxy)-3-bromo1 -(pyridin-3-ylmethyl)pyridin-2(1 H)-one; 4-(2,4-difluorobenzyloxy)-3-bromo1 -(pyridin-2-ylmethyl)pyridin-2(1 H)-one; 3-Chloro-4-(2,4-difluorobenzyloxy)-6-methyl1 -( 1H-pyrazol-4-ylmethyi)- 1 Hpyridin-2-one; 4-(Benzyloxy)-3-bromo1 -[(6-fluoropyridin-3-yl)methyl]pyridin-2( 1 H)-one; 1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one trifluoroacetate; 1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-bromo-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one hydrochloride; di fluorobenzyl)oxy]-6-methylpyridin-2(1H)-one trifluoroacetate; 1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-chloro-4-[(2,4difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one hydrochloride; 3-Bromo-4- [(2,4-difluorobenzyl)oxy]- 1 -( 1 H-indazol-5-ylmethyl)-6methylpyridin-2(1H)-one trifluoroacetate; 4- {[2-(Aminomethyl)-4-fluorobenzyl]oxy}-3-bromo1-(2,6-difluorophenyl)-6methylpyridin-2(l H)-one trifluoroacetate; Methyl 4- {[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1 (2H)- yl]methyl} pyrimidine-2-carboxylate trifluoroacetate; 3-Bromo-4-[(2,4-difluorobenzyl)oxy]- 1-[(2-hydroxypyrimidin-4-yl)methyl]-6methylpyridin-2(l H)-one trifluoroacetate; 4- { [3-bromo-4-[(2,4-di fluorobenzyl)ox y]-6-methyl-2-oxopyridin1 (2H)- yl]methyl } pyrimidine-2-carboxamide trifluoroacetate; Methyl (4- {[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}pyrimidin-2-yl)methylcarbamate; 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-[(5-methylpyrazin-2yl)methyl]pyridin-2(1 H)-one; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-(pyrazin-2-ylmethyl)pyridin2(1H)-one; 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-l- {[5-(hydroxymethyl)pyrazin-2yl] methyl } -6-methylpyridin-2(1H)-one; 3-Bromo-4- [(2,4-difluorobenzyl)oxy]- 1 -( { 5-[(dimethylamino)methyl] pyrazin-2yl } methyl)-6-methylpyridin-2(1H)-one tri fluoroacetate; 3-Bromo-4-[(2,4-difluorobenzyl)oxy]- 1-[(5-{[(2-hydroxyethyl)(methyl)amino]- methyl } pyrazin-2-yl)methyl]-6-methylpyridin-2( 1H)-one tri fluoroacetate; 5- {[3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1 (2H)- yl] methyl } -N-(2-hydroxyethyl)-N-methylpyrazi ne-2-carboxamide; 5- { [3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}-N-(2,3-dihydroxypropyl)pyrazine-2-carboxamide; 5- { [3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl] methyl } -N-(2-hydroxyethyl)p yrazine-2-carboxamide; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-(pyridin-4-ylmethyl)pyridin3-bromo-4-[(2,4-di fluorobenzyl)oxy]-6-methyl1-(pyridin-3-ylmethyl)pyridin2(lH)-one, 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-(pyridin-2-ylmethyl)pyridin2(1H)-one, 4-(4fluorobenzyloxy)-3-bromo-6-methyl1 -(pyridin-4-ylmethyl)pyridin-2( 1 H)- one; 4-(2,6-di fluorobenzyloxy)-3-bromo-6-methyl1 -(pyridin-4-ylmethyl)pyridin2(lH)-one; 4-(2,4,6-trifluorobenzyloxy)-3-bromo-6-methyl1 -(pyridin-4-ylmethyl)pyridin2(1H)-one; 4-(4-fluorobenzyloxy)-3-bromo-6-methyl-l-(pyridin-3-ylmethyl)pyridin-2(1 H)- one; 4-(2,4,6-trifluorobenzyloxy)-3-bromo-6-methyl1 -(pyridin-3-ylmethyl)pyridin2(1H)-one, 4-(2-fluorobenzyloxy)-3-bromo-6-methyl1 -(pyridin-3-ylmethyl)pyridin-2( 1 H)- one; 4-(2,4,5-trifluorobenzyloxy)-3-bromo-6-methyl1 -(pyridin-3-ylmethyl)pyridin2(1H)-one; 4-(4-chloro-2-fluorobenzyloxy)-3-bromo-6-methyl-l-(pyridin-3ylmethyl)pyridin-2(1 H)-one; 4-(2-chloro-4-fluorobenzyloxy)-3-bromo-6-methyl-l-(pyridin-3ylmethyl)pyridin-2(1H)-one; 4-(2-chloro-4-fluorobenzyloxy)-3-bromo-6-methyl-l-(pyridin-3ylmethyl)pyridin-2(1H)-one; 4-(4-fluorobenzyloxy)-3-bromo-6-methyl-l-(pyridin-2-ylmethyl)pyridin-2(1 H)- one; 4-(2,4,6-trifluorobenzyloxy)-3-bromo-6-methyl-l-(pyridin-2-ylmethyl)pyridin2(1H)-one; 4-(2,4,5-tri fluorobenzyloxy)-3-bromo-6-methyl1 - (pyridin-2-ylmethyl)pyridin2(1H)-one; 3-bromo-4-[2-(4-fluorophenyl)ethyl]-6-methyl1 -(pyridin-3-ylmethyl)pyridin2(1H)-one; 3-bromo-4-[2-(4-fluorophenyl)ethyl]-6-methyl1 -(pyridin-4-ylmethyl)pyridin3-chloro-4- [(2,4-difluorobenzyl)oxy]-6-methyl1 -(pyridin-3-ylmethyl)pyridin2(lH)-one; 1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-bromo-6-methyl-4-[(2,4,6trifluorobenzyl)oxy]pyridin-2(1H)-one trifluoroacetate; 3 -bromo-4- [(2,4-di fluorobenzyl)ox y] -6-methyl1 - { [2-methyl-4- (methylamino)pyrimidin-5-yl]methyl} pyridin-2(1H)-one trifluoroacetate; 3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-l-[(5-methylpyrazin-2yl)methyl] pyridin-2(1 H)-one; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl1-({5- [(methylamino)methyl]pyrazin-2-yl} methyl)pyridin-2(1H)-one trifluoroacetate; ethyl 5- { [3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl } pyrazine-2-carbox ylate; 3-chloro-4-[(2,4-difluorobenzyl)oxy]- 1 - { [5-(hydroxymethyl)pyrazin-2yl]methyl}-6-methylpyridin-2(1 H)-one; 5- { [3-bromo-4- [(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}-N,N-dimethylpyrazine-2-carboxamide; 5- { [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}-N-methylpyrazine-2-carboxamide; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-l- {[5-(1-hydroxy-l-methylethyl)pyrazin2-yl] methyl} -6-meth ylp yridin-2( 1 H)-one; 5- { [3-bromo-4-[(2,4-di fluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}-N-(2-methoxyethyl)pyrazine-2-carboxamide; 5- { [3-chloro-4-[(2,4-di fluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}-N-(2,2,2-trifluoroethyl)pyrazine-2-carboxamide; 4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-l-(pyridin-3-ylmethyl)pyridin2(1H)-one; 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-l-(pyridin-3ylmethyl)pyridin-2(1 H)-one; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6- [(dimethylamino)methyl]- 1-(pyridin-3ylmethyl)pyridin-2(1H)-one; 3-bromo-4- [(2,4-difluorobenzyl)amino]-6-methyl1-(pyridin-4-ylmethyl)pyridin2(1H)-one; 3-bromo-4- [(2,4-difluorobenzyl)amino]-6-methyl1 -(pyridin-3-ylmethyl)pyridin3-bromo-4-[(2,4-difluorobenzyl)oxy]- 1- {[5-(1-hydroxy-l-methylethyl)pyridin-2yl]methyl}-6-methylpyridin-2(1H)-one; 3-bromo-4-[(2,4-di fluorobenzyl)oxy]- 1 - { [5-(hydroxymethyl)pyridin-2yl]methyl}-6-methylpyridin-2(1H)-one; 6- { [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}-N-(2-hydroxyethyl)-N-methylnicotinamide; 6- { [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}-N-(2-hydroxyethyl)nicotinamide; 6- {[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}-N,N-dimethylnicotinamide; ethyl 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxo-2H-1,2'-bipyridine5'-carboxylate; 3-bromo-4-[(2,4-difluorobenzyl)oxy]-5'-(1-hydroxy1-methylethyl)-6-methyl2H1,2'-bipyridin-2-one; 3-bromo-4-[(2,4-di fluorobenzyi)oxy]- 1 -(2furylmethyl)-6-methylpyridin-2(1 H)- one; 3-Chloro-4-(2,4-difluorobenzyloxy)-6-methyl-l-(1 H-pyrazol-3-ylmethyl)- 1Hpyridin-2-one; 3-Chloro-4-(2,4-di fluorobenzyloxy)-6-methyl1 -(2,3-dihydro1 H-indol-5ylmethyl)- 1H-pyridin-2-one; Methyl (5- { [3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)-yl]methyl} pyrazin-2-yl)methyl(methyl)earbamate; N-I(5- { [3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl] methyl } pyrazin-2-yl)methyl]-2-hydroxy-N,2-dimethylpropanamide; 5- { [3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}-N-(2-hydroxy-2-methylpropyl)pyrazine-2-carboxamide; 1 -[(5-Aminopyrazin-2-yl)methyl]-3-bromo-4-[(2,4-difluorobenzyi)oxy]-6methylpyridin-2(1H)-one trifluoroacetate; 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl1 -[(3-methyl1,2,4-triazin-6yl)methyl]pyridin-2(l H)-one trifluoroacetate; 3-Bromo-4-[(2,4-difluorobenzyl)oxy]- 1 -( 1H-indazol-5-yl)-6-methylpyridin2(1H)-one; 3-bromo-4-[(2,4-difluorobenzyl)oxy]- 1 -( 1 H-indazol-6-yl)-6-methylp yridinmethyl 5- { [3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)- yl]methyl}-2-furoate; 4-(2,4-difl uorobenzyloxy)-3-chloro-6-methyl1 -((5-methylpyrazin-2yl)methyl)pyridin-2(1 H)-one; 4-(2,4-difluorobenzyloxy)-3-chloro-1 -((5-(hydroxymethyl)pyrazin-2-yl)methyl)- 6-methylpyridin-2(1H)-one; 4-(2,4-difluorobenzyloxy)-3-bromo-1 -(indolin-5-ylmethyl)-6-methylpyridin2(1H)-one; 1-((1 H-pyrazol-3-yl)methyl)-4-(4-fluoro-2-methylbenzyloxy)-3-bromo-6methylpyridin-2(1H)-one; 4-(2,4-di fluorobenzyloxy)- 1 -((2-(aminomethyl)-4-methylp yrimidin5- yl)methyl)-3-bromo-6-methylpyridin-2( 1H)-one; 4-(2,4-di fluorobenzyloxy)-3-bromo1 -((2-((dimethylamino)methyl)-4methylpyrimidin-5yl)methyl)-6-methylpyridin-2 ( 1H)-one; 5-((4-(2,4-di fluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin1 (2H)- yl)methyl)-4-methylpyrimidine-2-carboxamide; 5-((4-(2,4-di fluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin1 (2H)- yl)methyl)-N,4-dimethylpyrimidine-2-carboxamide; 5- {[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1 (2H)- yl] methyl } -2furamide; 5-[3-bromo-4-[(2,4-di fluorobenzyl)oxy]-6-methyl-2-oxopyridin1 (2H)-yl]-2furamide; 5- { [3-chloro-4-[(2,4-di fl uorobenzyl)ox y]-6-methyl-2-oxopyridin1 (2H)- yl]methyl }-N,N-dimethylindoline1 -carboxamide; and 5- { [ 3 -chloro-4-[(2,4-di fl uorobenzyl)oxy] 2-oxopyridin1 (2H)-yl] methyl } -N, N-dimethylindoline1 -carboxamide.

20. The use of a compound according to any one of claims 1 to 15 in the manufacture of a medicament for treating a TNF mediated disorder, a p38 kinase mediated disorder, inflammation and/or arthritis.

Dated 27 November, 2008 Pharmacia Corporation Patent Attorneys for the Applicant/Nominated Person SPRUSON & FERGUSON



Цитирование НПИ

GB 1289187
US 3654291
US 3715358
US 6344323
WO 1997/010712
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